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Molecular Cancer
Published in: Molecular Cancer 1/2020

Open Access 01-12-2020 | Review

The role of ubiquitination and deubiquitination in cancer metabolism

Authors: Tianshui Sun, Zhuonan Liu, Qing Yang

Published in: Molecular Cancer | Issue 1/2020

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Abstract

Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.
Literature
1.
2.
Lunt SY, Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol. 2011;27:441–64.PubMedCrossRef
3.
Faubert B, Li KY, Cai L, Hensley CT, Kim J, Zacharias LG, Yang C, Do QN, Doucette S, Burguete D, et al. Lactate metabolism in human lung tumors. Cell. 2017;171:358–371 e359.PubMedPubMedCentralCrossRef
4.
Moreau P, Attal M, Caillot D, Macro M, Karlin L, Garderet L, Facon T, Benboubker L, Escoffre-Barbe M, Stoppa AM, et al. Prospective evaluation of magnetic resonance imaging and [(18)F]Fluorodeoxyglucose positron emission tomography-computed tomography at diagnosis and before maintenance therapy in symptomatic patients with multiple myeloma included in the IFM/DFCI 2009 trial: results of the IMAJEM study. J Clin Oncol. 2017;35:2911–8.PubMedPubMedCentralCrossRef
5.
Xie H, Hanai J, Ren JG, Kats L, Burgess K, Bhargava P, Signoretti S, Billiard J, Duffy KJ, Grant A, et al. Targeting lactate dehydrogenase--a inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor-initiating cells. Cell Metab. 2014;19:795–809.PubMedPubMedCentralCrossRef
6.
Wang YH, Israelsen WJ, Lee D, Yu VWC, Jeanson NT, Clish CB, Cantley LC, Vander Heiden MG, Scadden DT. Cell-state-specific metabolic dependency in hematopoiesis and leukemogenesis. Cell. 2014;158:1309–23.PubMedPubMedCentralCrossRef
7.
Antao AM, Tyagi A, Kim KS, Ramakrishna S. Advances in deubiquitinating enzyme inhibition and applications in cancer therapeutics. Cancers (Basel). 2020;12.
8.
Park HB, Kim JW, Baek KH. Regulation of Wnt signaling through ubiquitination and deubiquitination in cancers. Int J Mol Sci. 2020;21.
9.
10.
11.
Deng L, Meng T, Chen L, Wei W, Wang P. The role of ubiquitination in tumorigenesis and targeted drug discovery. Signal Transduct Target Ther. 2020;5:11.PubMedPubMedCentralCrossRef
12.
13.
Dibble CC, Manning BD. Signal integration by mTORC1 coordinates nutrient input with biosynthetic output. Nat Cell Biol. 2013;15:555–64.PubMedPubMedCentral
14.
Dutchak PA, Estill-Terpack SJ, Plec AA, Zhao X, Yang C, Chen J, Ko B, Deberardinis RJ, Yu Y, Tu BP. Loss of a negative regulator of mTORC1 induces aerobic glycolysis and altered fiber composition in skeletal muscle. Cell Rep. 2018;23:1907–14.PubMedPubMedCentralCrossRef
15.
Csibi A, Fendt SM, Li C, Poulogiannis G, Choo AY, Chapski DJ, Jeong SM, Dempsey JM, Parkhitko A, Morrison T, et al. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell. 2013;153:840–54.PubMedPubMedCentralCrossRef
16.
Mikalayeva V, Cesleviciene I, Sarapiniene I, Zvikas V, Skeberdis VA, Jakstas V, Bordel S. Fatty acid synthesis and degradation interplay to regulate the oxidative stress in cancer cells. Int J Mol Sci. 2019;20.
17.
Barker RM, Holly JMP, Biernacka KM, Allen-Birt SJ, Perks CM. Mini review: opposing pathologies in cancer and alzheimer’s disease: does the PI3K/Akt pathway provide clues? Front Endocrinol (Lausanne). 2020;11:403.CrossRef
18.
Holczer M, Hajdu B, Lorincz T, Szarka A, Banhegyi G, Kapuy O. A double negative feedback loop between mTORC1 and AMPK kinases guarantees precise autophagy induction upon cellular stress. Int J Mol Sci. 2019;20.
19.
Zhao XA, Petrashen AP, Sanders JA, Peterson AL, Sedivy JM. SLC1A5 glutamine transporter is a target of MYC and mediates reduced mTORC1 signaling and increased fatty acid oxidation in long-lived Myc hypomorphic mice. Aging Cell. 2019;18.
20.
Maddocks ODK, Berkers CR, Mason SM, Zheng L, Blyth K, Gottlieb E, Vousden KH. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature. 2013;493:542.PubMedCrossRef
21.
Kim D, Fiske BP, Birsoy K, Freinkman E, Kami K, Possemato RL, Chudnovsky Y, Pacold ME, Chen WW, Cantor JR, et al. SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance. Nature. 2015;520:363-+.PubMedPubMedCentralCrossRef
22.
Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020;21:363–83.PubMedCrossRef
23.
Li X, Liang M, Jiang JX, He RZ, Wang M, Guo XJ, Shen M, Qin RY. Combined inhibition of autophagy and Nrf2 signaling augments bortezomib-induced apoptosis by increasing ROS production and ER stress in pancreatic cancer cells. Int J Biol Sci. 2018;14:1291–305.PubMedPubMedCentralCrossRef
24.
Khan MS, Hwang J, Lee K, Choi Y, Seo Y, Jeon H, Hong JW, Choi J. Anti-tumor drug-loaded oxygen nanobubbles for the degradation of HIF-1 alpha and the upregulation of reactive oxygen species in tumor cells. Cancers. 2019;11.
25.
Follo C, Vidoni C, Morani F, Ferraresi A, Seca C, Isidoro C. Amino acid response by halofuginone in cancer cells triggers autophagy through proteasome degradation of mTOR. Cell Commun Signal. 2019;17.
26.
Yu L, Chen Y, Tooze SA. Autophagy pathway: cellular and molecular mechanisms. Autophagy. 2018;14:207–15.PubMedCrossRef
27.
Lock R, Roy S, Kenific CM, Su JS, Salas E, Ronen SM, Debnath J. Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Mol Biol Cell. 2011;22:165–78.PubMedPubMedCentralCrossRef
28.
Zhang C, Lin M, Wu R, Wang X, Yang B, Levine AJ, Hu W, Feng Z. Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect. Proc Natl Acad Sci U S A. 2011;108:16259–64.PubMedPubMedCentralCrossRef
29.
Martinez-Outschoorn UE, Pavlides S, Howell A, Pestell RG, Tanowitz HB, Sotgia F, Lisanti MP. Stromal-epithelial metabolic coupling in cancer: integrating autophagy and metabolism in the tumor microenvironment. Int J Biochem Cell Biol. 2011;43:1045–51.PubMedPubMedCentralCrossRef
30.
31.
Sewduth RN, Baietti MF, Sablina AA. Cracking the monoubiquitin code of genetic diseases. Int J Mol Sci. 2020;21.
32.
Baur R, Rape M. Getting close: insight into the structure and function of K11/K48-branched ubiquitin chains. Structure. 2020;28:1–3.PubMedCrossRef
33.
34.
Flick K, Raasi S, Zhang H, Yen JL, Kaiser P. A ubiquitin-interacting motif protects polyubiquitinated Met4 from degradation by the 26S proteasome. Nat Cell Biol. 2006;8:509–15.PubMedCrossRef
35.
Le Cam L, Linares LK, Paul C, Julien E, Lacroix M, Hatchi E, Triboulet R, Bossis G, Shmueli A, Rodriguez MS, et al. E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation. Cell. 2006;127:775–88.PubMedCrossRef
36.
Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002;82:373–428.PubMedCrossRef
37.
Tang R, Langdon WY, Zhang J. Regulation of immune responses by E3 ubiquitin ligase Cbl-b. Cell Immunol. 2019;340.
38.
Popovic D, Vucic D, Dikic I. Ubiquitination in disease pathogenesis and treatment. Nat Med. 2014;20:1242–53.PubMedCrossRef
39.
Rogers-Broadway KR, Kumar J, Sisu C, Wander G, Mazey E, Jeyaneethi J, Pados G, Tsolakidis D, Klonos E, Grunt T, et al. Differential expression of mTOR components in endometriosis and ovarian cancer: effects of rapalogues and dual kinase inhibitors on mTORC1 and mTORC2 stoichiometry. Int J Mol Med. 2019;43:47–56.PubMed
40.
Wang P, Zhang Q, Tan L, Xu YN, Xie XB, Zhao Y. The regulatory effects of mTOR complexes in the differentiation and function of CD4(+) T cell subsets. J Immunol Res. 2020;2020.
41.
Rogala KB, Gu X, Kedir JF, Abu-Remaileh M, Bianchi LF, Bottino AMS, Dueholm R, Niehaus A, Overwijn D, Fils ACP, et al. Structural basis for the docking of mTORC1 on the lysosomal surface. Science. 2019;366:468-+.PubMedPubMedCentralCrossRef
42.
Linares JF, Duran A, Yajima T, Pasparakis M, Moscat J, Diaz-Meco MT. K63 polyubiquitination and activation of mTOR by the p62-TRAF6 complex in nutrient-activated cells. Mol Cell. 2013;51:283–96.PubMedPubMedCentralCrossRef
43.
Mao JH, Kim IJ, Wu D, Climent J, Kang HC, DelRosario R, Balmain A. FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression. Science. 2008;321:1499–502.PubMedPubMedCentralCrossRef
44.
Wang FF, Zhang XJ, Yan YR, Zhu XH, Yu J, Ding Y, Hu JL, Zhou WJ, Zeng ZC, Liao WT, et al. FBX8 is a metastasis suppressor downstream of miR-223 and targeting mTOR for degradation in colorectal carcinoma. Cancer Lett. 2017;388:85–95.PubMedCrossRef
45.
Mimoto R, Nihira NT, Hirooka S, Takeyama H, Yoshida K. Diminished DYRK2 sensitizes hormone receptor-positive breast cancer to everolimus by the escape from degrading mTOR. Cancer Lett. 2017;384:27–38.PubMedCrossRef
46.
Kim SY, Kim HJ, Kim HJ, Kim CH. Non-thermal plasma induces antileukemic effect through mTOR ubiquitination. Cells. 2020;9.
47.
Park D, Lee MN, Jeong H, Koh A, Yang YR, Suh PG, Ryu SH. Parkin ubiquitinates mTOR to regulate mTORC1 activity under mitochondrial stress. Cell Signal. 2014;26:2122–30.PubMedCrossRef
48.
Agrawal P, Chen YT, Schilling B, Gibson BW, Hughes RE. Ubiquitin-specific peptidase 9, X-linked (USP9X) modulates activity of mammalian target of rapamycin (mTOR). J Biol Chem. 2012;287:21164–75.PubMedPubMedCentralCrossRef
49.
Hussain S, Feldman AL, Das C, Ziesmer SC, Ansell SM, Galardy PJ. Ubiquitin hydrolase UCH-L1 destabilizes mTOR complex 1 by antagonizing DDB1-CUL4-mediated ubiquitination of raptor. Mol Cell Biol. 2013;33:1188–97.PubMedPubMedCentralCrossRef
50.
Wang B, Jie ZL, Joo DH, Ordureau A, Liu P, Gan WJ, Guo JP, Zhang JF, North BJ, Dai XP, et al. TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2 signalling. Nature. 2017;545:365-+.PubMedPubMedCentralCrossRef
51.
Carbonneau M, Gagne LM, Lalonde ME, Germain MA, Motorina A, Guiot MC, Secco B, Vincent EE, Tumber A, Hulea L, et al. The oncometabolite 2-hydroxyglutarate activates the mTOR signalling pathway. Nat Commun. 2016;7.
52.
Chen L, Liu TY, Tu YH, Rong DY, Cao Y. Cul1 promotes melanoma cell proliferation by promoting DEPTOR degradation and enhancing cap-dependent translation. Oncol Rep. 2016;35:1049–56.PubMedCrossRef
53.
Tan MJ, Xu J, Siddiqui J, Feng FL, Sun Y. Depletion of SAG/RBX2 E3 ubiquitin ligase suppresses prostate tumorigenesis via inactivation of the PI3K/AKT/mTOR axis. Mol Cancer. 2016;15.
54.
Zhao LL, Wang XB, Yu Y, Deng L, Chen L, Peng XP, Jiao CC, Gao GL, Tan X, Pan WJ, et al. OTUB1 protein suppresses mTOR complex 1 (mTORC1) activity by deubiquitinating the mTORC1 inhibitor DEPTOR. J Biol Chem. 2018;293:4883–92.PubMedPubMedCentralCrossRef
55.
Antonioli M, Albiero F, Nazio F, Vescovo T, Perdomo AB, Corazzari M, Marsella C, Piselli P, Gretzmeier C, Dengjel J, et al. AMBRA1 interplay with cullin E3 ubiquitin ligases regulates autophagy dynamics. Dev Cell. 2014;31:734–46.PubMedCrossRef
56.
Luo ZG, Pan YF, Jeong LS, Liu J, Jia LJ. Inactivation of the cullin (CUL)-RING E3 ligase by the NEDD8-activating enzyme inhibitor MLN4924 triggers protective autophagy in cancer cells. Autophagy. 2012;8:1677–9.PubMedPubMedCentralCrossRef
57.
Feng JB, Zhang Y, Ren X, Li D, Fu HJ, Liu CH, Zhou W, Liu Q, Liu Q, Wu MH. Leucine-rich repeat containing 4 act as an autophagy inhibitor that restores sensitivity of glioblastoma to temozolomide. Oncogene. 2020;39:4551–66.PubMedPubMedCentralCrossRef
58.
Deng L, Jiang C, Chen L, Jin J, Wei J, Zhao L, Chen M, Pan W, Xu Y, Chu H, et al. The ubiquitination of rag A GTPase by RNF152 negatively regulates mTORC1 activation. Mol Cell. 2015;58:804–18.PubMedCrossRef
59.
Jin GX, Lee SW, Zhang X, Cai Z, Gao Y, Chou PC, Rezaeian AH, Han F, Wang CY, Yao JC, et al. Skp2-mediated RagA ubiquitination elicits a negative feedback to prevent amino-acid-dependent mTORC1 hyperactivation by recruiting GATOR1. Mol Cell. 2015;58:989–1000.PubMedPubMedCentralCrossRef
60.
Chen J, Ou YH, Yang YY, Li W, Xu Y, Xie YT, Liu Y. KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing. Nature. 2018;557:585.PubMedCrossRef
61.
Deng L, Chen L, Zhao LL, Xu Y, Peng XP, Wang XB, Ding L, Jin JL, Teng HQ, Wang YM, et al. Ubiquitination of Rheb governs growth factor-induced mTORC1 activation. Cell Res. 2019;29:136–50.PubMedCrossRef
62.
Guo P, Ma X, Zhao W, Huai W, Li T, Qiu Y, Zhang Y, Han L. TRIM31 is upregulated in hepatocellular carcinoma and promotes disease progression by inducing ubiquitination of TSC1-TSC2 complex. Oncogene. 2018;37:478–88.PubMedCrossRef
63.
Hu J, Zacharek S, He YJ, Lee H, Shumway S, Duronio RJ, Xiong Y. WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase. Genes Dev. 2008;22:866–71.PubMedPubMedCentralCrossRef
64.
Han S, Witt RM, Santos TM, Polizzano C, Sabatini BL, Ramesh V. Pam (protein associated with Myc) functions as an E3 ubiquitin ligase and regulates TSC/mTOR signaling. Cell Signal. 2008;20:1084–91.PubMedPubMedCentralCrossRef
65.
Zheng L, Ding HR, Lu ZM, Li Y, Pan YQ, Ning T, Ke Y. E3 ubiquitin ligase E6AP-mediated TSC2 turnover in the presence and absence of HPV16 E6. Genes Cells. 2008;13:285–94.PubMedCrossRef
66.
Chong-Kopera H, Inoki K, Li Y, Zhu TQ, Garcia-Gonzalo FR, Rosa JL, Guan KL. TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase. J Biol Chem. 2006;281:8313–6.PubMedCrossRef
67.
Mohan N, Shen Y, Dokmanovic M, Endo Y, Hirsch DS, Wu WJ. VPS34 regulates TSC1/TSC2 heterodimer to mediate RheB and mTORC1/S6K1 activation and cellular transformation. Oncotarget. 2016;7:52239–54.PubMedPubMedCentralCrossRef
68.
Madigan JP, Hou F, Ye LL, Hu JC, Dong AP, Tempel W, Yohe ME, Randazzo PA, Jenkins LMM, Gottesman MM, Tong YF. The tuberous sclerosis complex subunit TBC1D7 is stabilized by Akt phosphorylation-mediated 14–3-3 binding. J Biol Chem. 2018;293:16142–59.PubMedPubMedCentralCrossRef
69.
Rodriguez-Escudero I, Roelants FM, Thorner J, Nombela C, Molina M, Cid VJ. Reconstitution of the mammalian PI3K/PTEN/Akt pathway in yeast. Biochem J. 2005;390:613–23.PubMedPubMedCentralCrossRef
70.
Wang ZX, Dang TT, Liu TT, Chen S, Li L, Huang S, Fang M. NEDD4L protein catalyzes ubiquitination of PIK3CA protein and regulates PI3K-AKT signaling. J Biol Chem. 2016;291:17467–77.PubMedPubMedCentralCrossRef
71.
Hamidi A, Song J, Thakur N, Itoh S, Marcusson A, Bergh A, Heldin CH, Landstrom M. TGF-beta promotes PI3K-AKT signaling and prostate cancer cell migration through the TRAF6-mediated ubiquitylation of p85 alpha. Sci Signal. 2017;10.
72.
Jiang J, Xu YT, Ren HJ, Wudu M, Wang QZ, Song X, Su HB, Jiang XZ, Jiang LH, Qiu XS. MKRN2 inhibits migration and invasion of non-small-cell lung cancer by negatively regulating the PI3K/Akt pathway. J Exp Clin Cancer Res. 2018;37.
73.
Ko HR, Kim CK, Lee SB, Song J, Lee KH, Kim KK, Park KW, Cho SW, Ahn JY. P42 Ebp1 regulates the proteasomal degradation of the p85 regulatory subunit of PI3K by recruiting a chaperone-E3 ligase complex HSP70/CHIP. Cell Death Dis. 2014;5.
74.
Kuchay S, Duan SS, Schenkein E, Peschiaroli A, Saraf A, Florens L, Washburn MP, Pagano M. FBXL2-and PTPL1-mediated degradation of p110-free p85 beta regulatory subunit controls the PI(3)K signalling cascade. Nat Cell Biol. 2013;15:472-+.PubMedCrossRef
75.
Wu YH, Chang TH, Huang YF, Chen CC, Chou CY. COL11A1 confers chemoresistance on ovarian cancer cells through the activation of Akt/c/EBP beta pathway and PDK1 stabilization. Oncotarget. 2015;6:23748–63.PubMedPubMedCentralCrossRef
76.
Uras IZ, List T, Nijman SMB. Ubiquitin-specific protease 4 inhibits mono-ubiquitination of the master growth factor signaling kinase PDK1. PLoS One. 2012;7.
77.
Chan CH, Li CF, Yang WL, Gao Y, Lee SW, Feng ZZ, Huang HY, Tsai KKC, Flores LG, Shao YP, et al. The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis (vol 149, pg 1098, 2012). Cell. 2012;151:913–4.CrossRefPubMed
78.
Yang WL, Wang J, Chan CH, Lee SW, Campos AD, Lamothe B, Hur L, Grabiner BC, Lin X, Darnay BG, Lin HK. The E3 ligase TRAF6 regulates Akt ubiquitination and activation. Science. 2009;325:1134–8.PubMedPubMedCentralCrossRef
79.
Fan CD, Lum MA, Xu C, Black JD, Wang XJ. Ubiquitin-dependent regulation of phospho-AKT dynamics by the ubiquitin E3 ligase, NEDD4–1, in the insulin-like growth factor-1 response. J Biol Chem. 2013;288:1674–84.PubMedCrossRef
80.
Li W, Peng C, Lee MH, Lim D, Zhu F, Fu Y, Yang G, Sheng YQ, Xiao LB, Dong X, et al. TRAF4 is a critical molecule for Akt activation in lung cancer. Cancer Res. 2013;73:6938–50.PubMedCrossRef
81.
Zhang JD, Yang ZF, Ou JY, Xia XJ, Zhi F, Cui J. The F-box protein FBXL18 promotes glioma progression by promoting K63-linked ubiquitination of Akt. FEBS Lett. 2017;591:145–54.PubMedCrossRef
82.
Liang CX, Liang GY, Zheng XQ, Huang YX, Huang SH, Yin D. RSP5 positively regulates the osteogenic differentiation of mesenchymal stem cells by activating the K63-linked ubiquitination of Akt. Stem Cells Int. 2020;2020.
83.
Wang GH, Long J, Gao Y, Zhang WN, Han F, Xu C, Sun L, Yang SC, Lan JQ, Hou ZL, et al. SETDB1-mediated methylation of Akt promotes its K63-linked ubiquitination and activation leading to tumorigenesis. Nat Cell Biol. 2019;21:214.PubMedPubMedCentralCrossRef
84.
Li HJ, Lan JQ, Wang GH, Guo KX, Han CS, Li XL, Hu JB, Cao ZX, Luo XL. KDM4B facilitates colorectal cancer growth and glucose metabolism by stimulating TRAF6-mediated AKT activation. J Exp Clin Cancer Res. 2020;39.
85.
Lim JH, Jono H, Komatsu K, Woo CH, Lee J, Miyata M, Matsuno T, Xu XB, Huang YX, Zhang WH, et al. CYLD negatively regulates transforming growth factor-beta-signalling via deubiquitinating Akt. Nat Commun. 2012;3.
86.
Yin FL, He HG, Zhang B, Zheng JH, Wang M, Zhang M, Cui HX. Effect of deubiquitinase ovarian tumor domain-containing protein 5 (OTUD5) on radiosensitivity of cervical cancer by regulating the ubiquitination of Akt and its mechanism. Med Sci Monit. 2019;25:3469–75.PubMedPubMedCentralCrossRef
87.
Goldbraikh D, Neufeld D, Eid-Mutlak Y, Lasry I, Gilda JE, Parnis A, Cohen S. USP1 deubiquitinates Akt to inhibit PI3K-Akt-FoxO signaling in muscle during prolonged starvation. EMBO Rep. 2020;21.
88.
Qiu CJ, Liu KR, Zhang S, Gao SM, Chen WR, Li DT, Huang YX. Bisdemethoxycurcumin inhibits hepatocellular carcinoma proliferation through Akt inactivation via CYLD-mediated deubiquitination. Drug Des Devel Ther. 2020;14:993–1001.PubMedPubMedCentralCrossRef
89.
90.
Suizu F, Hiramuki Y, Okumura F, Matsuda M, Okumura AJ, Hirata N, Narita M, Kohno T, Yokota J, Bohgaki M, et al. The E3 ligase TTC3 facilitates ubiquitination and degradation of phosphorylated Akt. Dev Cell. 2009;17:800–10.PubMedCrossRef
91.
Joo HM, Kim JY, Jeong JB, Seong KM, Nam SY, Yang KH, Kim CS, Kim HS, Jeong M, An S, Jin YW. Ret finger protein 2 enhances ionizing radiation-induced apoptosis via degradation of AKT and MDM2. Eur J Cell Biol. 2011;90:420–31.PubMedCrossRef
92.
Bae SH, Kim SY, Jung JH, Yoon YM, Cha HJ, Lee HJ, Kim K, Kim J, An IS, Kim J, et al. Akt is negatively regulated by the MULAN E3 ligase. Cell Res. 2012;22:873–85.PubMedPubMedCentralCrossRef
93.
Su CH, Wang CY, Lan KH, Li CP, Chao Y, Lin HC, Lee SD, Lee WP. Akt phosphorylation at Thr308 and Ser473 is required for CHIP-mediated ubiquitination of the kinase. Cell Signal. 2011;23:1824–30.PubMedCrossRef
94.
Wakatsuki S, Saitoh F, Araki T. ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B-dependent CRMP2 phosphorylation. Nat Cell Biol. 2011;13:1415–U1259.PubMedCrossRef
95.
Athamneh K, El Hasasna H, Al Samri H, Attoub S, Arafat K, Benhalilou N, Al Rashedi A, Al Dhaheri Y, AbuQamar S, Eid A, Iratni R. Rhus coriaria increases protein ubiquitination, proteasomal degradation and triggers non-canonical Beclin-1-independent autophagy and apoptotic cell death in colon cancer cells. Sci Rep. 2017;7.
96.
Su X, Shen Z, Yang Q, Sui F, Pu J, Ma JJ, Ma SR, Yao DM, Ji MJ, Hou P. Vitamin C kills thyroid cancer cells through ROS-dependent inhibition of MAPK/ERK and PI3K/AKT pathways via distinct mechanisms. Theranostics. 2019;9:4461–73.PubMedPubMedCentralCrossRef
97.
Kim HJ, Kim SY, Kim DH, Park JS, Jeong SH, Choi YW, Kim CH. Crosstalk between HSPA5 arginylation and sequential ubiquitination leads to AKT degradation through autophagy flux. Autophagy. 2020.
98.
Trotman LC, Wang XJ, Alimonti A, Chen ZB, Teruya-Feldstein J, Yang HJ, Pavletich NP, Carver BS, Cordon-Cardo C, Erdjument-Bromage H, et al. Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell. 2007;128:141–56.PubMedPubMedCentralCrossRef
99.
Shen X, Zhong JX, Yu P, Zhao QY, Huang T. YY1-regulated LINC00152 promotes triple negative breast cancer progression by affecting on stability of PTEN protein. Biochem Biophys Res Commun. 2019;509:448–54.PubMedCrossRef
100.
Maddika S, Kavela S, Rani N, Palicharla VR, Pokorny JL, Sarkaria JN, Chen JJ. WWP2 is an E3 ubiquitin ligase for PTEN. Nat Cell Biol. 2011;13:728–U224.PubMedPubMedCentralCrossRef
101.
Yang H, Wang XX, Zhou CY, Xiao X, Tian C, Li HH, Yin CL, Wang HX. Tripartite motif 10 regulates cardiac hypertrophy by targeting the PTEN/AKT pathway. J Cell Mol Med. 2020;24:6233–41.PubMedPubMedCentralCrossRef
102.
Yuan P, Zheng AD, Tang Q. Tripartite motif protein 25 is associated with epirubicin resistance in hepatocellular carcinoma cells via regulating PTEN/AKT pathway. Cell Biol Int. 2020;44:1503–13.PubMedCrossRef
103.
He R, Liu HX. TRIM59 knockdown blocks cisplatin resistance in A549/DDP cells through regulating PTEN/AKT/HK2. Gene. 2020;747.
104.
Ma L, Yao NH, Chen P, Zhuang ZX. TRIM27 promotes the development of esophagus cancer via regulating PTEN/AKT signaling pathway. Cancer Cell Int. 2019;19.
105.
Shen WD, Jin ZH, Tong XP, Wang HY, Zhuang LL, Lu XF, Wu SB. TRIM14 promotes cell proliferation and inhibits apoptosis by suppressing PTEN in colorectal cancer. Cancer Manag Res. 2019;11:5725–35.PubMedPubMedCentralCrossRef
106.
Van Themsche C, Leblanc V, Parent S, Asselin E. X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization. J Biol Chem. 2009;284:20462–6.PubMedPubMedCentralCrossRef
107.
Lee MS, Jeong MH, Lee HW, Han HJ, Ko A, Hewitt SM, Kim JH, Chun KH, Chung JY, Lee C, et al. PI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis. Nat Commun. 2015;6.
108.
Lee YR, Chen M, Lee JD, Zhang J, Lin SY, Fu TM, Chen H, Ishikawa T, Chiang SY, Katon J, et al. Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway. Science. 2019;364.
109.
Lee JT, Shan J, Zhong JY, Li MY, Zhou B, Zhou A, Parsons R, Gu W. RFP-mediated ubiquitination of PTEN modulates its effect on AKT activation. Cell Res. 2013;23:552–64.PubMedPubMedCentralCrossRef
110.
Sun J, Li TX, Zhao YY, Huang LR, Sun H, Wu H, Jiang XF. USP10 inhibits lung cancer cell growth and invasion by upregulating PTEN. Mol Cell Biochem. 2018;441:1–7.PubMedCrossRef
111.
Zhang JS, Zhang PJ, Wei YK, Piao HL, Wang WQ, Maddika S, Wang M, Chen DH, Sun YT, Hung MC, et al. Deubiquitylation and stabilization of PTEN by USP13. Nat Cell Biol. 2013;15:1486.PubMedPubMedCentralCrossRef
112.
Yuan L, Lv YR, Li HC, Gao HD, Song SS, Zhang Y, Xing GC, Kong XZ, Wang LJ, Li Y, et al. Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis (vol 17, pg 1169, 2015). Nat Cell Biol. 2015;17.
113.
Shen WM, Yin JN, Xu RJ, Xu DF, Zheng SY. Ubiquitin specific peptidase 49 inhibits non-small cell lung cancer cell growth by suppressing PI3K/AKT signaling. Kaohsiung J Med Sci. 2019;35:401–7.PubMed
114.
Zhang H, Wei PT, Lv WW, Han XT, Yang JH, Qin SF. Long noncoding RNA lnc-DILC stabilizes PTEN and suppresses clear cell renal cell carcinoma progression. Cell Biosci. 2019;9.
115.
Morotti A, Panuzzo C, Crivellaro S, Pergolizzi B, Familiari U, Berger AH, Saglio G, Pandolfi PP. BCR-ABL disrupts PTEN nuclear-cytoplasmic shuttling through phosphorylation-dependent activation of HAUSP. Leukemia. 2014;28:1326–33.PubMedCrossRef
116.
Wu Y, Zhou H, Wu K, Lee S, Li RJ, Liu X. PTEN phosphorylation and nuclear export mediate free fatty acid-induced oxidative stress. Antioxid Redox Signal. 2014;20:1382–95.PubMedPubMedCentralCrossRef
117.
Sacco JJ, Yau TY, Darling S, Patel V, Liu H, Urbe S, Clague MJ, Coulson JM. The deubiquitylase Ataxin-3 restricts PTEN transcription in lung cancer cells. Oncogene. 2014;33:4265–72.PubMedCrossRef
118.
Pineda CT, Ramanathan S, Tacer KF, Weon JL, Potts MB, Ou YH, White MA, Potts PR. Degradation of AMPK by a cancer-specific ubiquitin ligase. Cell. 2015;160:715–28.PubMedPubMedCentralCrossRef
119.
Kwon E, Li X, Deng Y, Chang HW, Kim DY. AMPK is down-regulated by the CRL4A-CRBN axis through the polyubiquitination of AMPKalpha isoforms. FASEB J. 2019;33:6539–50.PubMedCrossRef
120.
121.
Yang SJ, Jeon SJ, Nguyen TV, Deshaies RJ, Park CS, Lee KM. Ubiquitin-dependent proteasomal degradation of AMPK gamma subunit by cereblon inhibits AMPK activity. Biochim Biophys Acta Mol Cell Res. 2020;1867.
122.
Liu HZ, Ding J, Kohnlein K, Urban N, Ori A, Villavicencio-Lorini P, Walentek P, Klotz LO, Hollemann T, Pfirrmann T. The GID ubiquitin ligase complex is a regulator of AMPK activity and organismal lifespan. Autophagy. 2019.
123.
Xu K, Park D, Magis AT, Zhang J, Zhou W, Sica GL, Ramalingam SS, Curran WJ, Deng XM. Small molecule KRAS agonist for mutant KRAS cancer therapy. Mol Cancer. 2019;18.
124.
Sasaki AT, Carracedo A, Locasale JW, Anastasiou D, Takeuchi K, Kahoud ER, Haviv S, Asara JM, Pandolfi PP, Cantley LC. Ubiquitination of K-Ras enhances activation and facilitates binding to select downstream effectors. Sci Signal. 2011;4.
125.
Abe T, Umeki I, Kanno S, Inoue S, Niihori T, Aoki Y. LZTR1 facilitates polyubiquitination and degradation of RAS-GTPases. Cell Death Differ. 2020;27:1023–35.PubMedCrossRef
126.
Zeng TL, Wang Q, Fu JY, Lin Q, Bi J, Ding WC, Qiao YK, Zhang S, Zhao WX, Lin HY, et al. Impeded Nedd4–1-mediated Ras degradation underlies Ras-driven tumorigenesis. Cell Rep. 2014;7:871–82.PubMedCrossRef
127.
Dang CV. The interplay between MYC and HIF in the Warburg effect. Ernst Schering Found Symp Proc. 2007:35–53.
128.
Buckley DL, Van Molle I, Gareiss PC, Tae HS, Michel J, Noblin DJ, Jorgensen WL, Ciulli A, Crews CM. Targeting the von Hippel-Lindau E3 ubiquitin ligase using small molecules to disrupt the VHL/HIF-1alpha interaction. J Am Chem Soc. 2012;134:4465–8.PubMedPubMedCentralCrossRef
129.
Guo Y, Meng X, Ma J, Zheng Y, Wang Q, Wang Y, Shang H. Human papillomavirus 16 E6 contributes HIF-1alpha induced Warburg effect by attenuating the VHL-HIF-1alpha interaction. Int J Mol Sci. 2014;15:7974–86.PubMedPubMedCentralCrossRef
130.
Liu J, Zhang C, Zhao YH, Yue XT, Wu H, Huang S, Chen J, Tomsky K, Xie HY, Khella CA, et al. Parkin targets HIF-1 alpha for ubiquitination and degradation to inhibit breast tumor progression. Nat Commun. 2017;8.
131.
Zhang L, Cao J, Dong L, Lin H. TiPARP forms nuclear condensates to degrade HIF-1alpha and suppress tumorigenesis. Proc Natl Acad Sci U S A. 2020;117:13447–56.PubMedPubMedCentralCrossRef
132.
Thirusangu P, Vigneshwaran V, Prashanth T, Vijay Avin BR, Malojirao VH, Rakesh H, Khanum SA, Mahmood R, Prabhakar BT. BP-1T, an antiangiogenic benzophenone-thiazole pharmacophore, counteracts HIF-1 signalling through p53/MDM2-mediated HIF-1alpha proteasomal degradation. Angiogenesis. 2017;20:55–71.PubMedCrossRef
133.
Joshi S, Singh AR, Durden DL. MDM2 regulates hypoxic hypoxia-inducible factor 1alpha stability in an E3 ligase, proteasome, and PTEN-phosphatidylinositol 3-kinase-AKT-dependent manner. J Biol Chem. 2014;289:22785–97.PubMedPubMedCentralCrossRef
134.
Chowdhury AR, Long A, Fuchs SY, Rustgi A, Avadhani NG. Mitochondrial stress-induced p53 attenuates HIF-1alpha activity by physical association and enhanced ubiquitination. Oncogene. 2017;36:397–409.PubMedCrossRef
135.
Amelio I, Inoue S, Markert EK, Levine AJ, Knight RA, Mak TW, Melino G. TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1alpha degradation. Proc Natl Acad Sci U S A. 2015;112:226–31.PubMedCrossRef
136.
Flugel D, Gorlach A, Kietzmann T. GSK-3beta regulates cell growth, migration, and angiogenesis via Fbw7 and USP28-dependent degradation of HIF-1alpha. Blood. 2012;119:1292–301.PubMedPubMedCentralCrossRef
137.
Lee SH, Jee JG, Bae JS, Liu KH, Lee YM. A group of novel HIF-1alpha inhibitors, glyceollins, blocks HIF-1alpha synthesis and decreases its stability via inhibition of the PI3K/AKT/mTOR pathway and Hsp90 binding. J Cell Physiol. 2015;230:853–62.PubMedCrossRef
138.
Lee YM, Kim GH, Park EJ, Oh TI, Lee S, Kan SY, Kang H, Kim BM, Kim JH, Lim JH. Thymoquinone selectively kills hypoxic renal cancer cells by suppressing HIF-1alpha-mediated glycolysis. Int J Mol Sci. 2019;20.
139.
Ju UI, Park JW, Park HS, Kim SJ, Chun YS. FBXO11 represses cellular response to hypoxia by destabilizing hypoxia-inducible factor-1alpha mRNA. Biochem Biophys Res Commun. 2015;464:1008–15.PubMedCrossRef
140.
Chen Z, Lin TC, Bi X, Lu G, Dawson BC, Miranda R, Medeiros LJ, McNiece I, McCarty N. TRIM44 promotes quiescent multiple myeloma cell occupancy and survival in the osteoblastic niche via HIF-1alpha stabilization. Leukemia. 2019;33:469–86.PubMedCrossRef
141.
Wu HT, Kuo YC, Hung JJ, Huang CH, Chen WY, Chou TY, Chen Y, Chen YJ, Chen YJ, Cheng WC, et al. K63-polyubiquitinated HAUSP deubiquitinates HIF-1alpha and dictates H3K56 acetylation promoting hypoxia-induced tumour progression. Nat Commun. 2016;7:13644.PubMedPubMedCentralCrossRef
142.
Park JJ, Yun JH, Baek KH. Polyclonal and monoclonal antibodies specific for ubiquitin-specific protease 20. Monoclon Antib Immunodiagn Immunother. 2013;32:193–9.PubMedCrossRef
143.
144.
Bremm A, Moniz S, Mader J, Rocha S, Komander D. Cezanne (OTUD7B) regulates HIF-1alpha homeostasis in a proteasome-independent manner. EMBO Rep. 2014;15:1268–77.PubMedPubMedCentralCrossRef
145.
Troilo A, Alexander I, Muehl S, Jaramillo D, Knobeloch KP, Krek W. HIF1alpha deubiquitination by USP8 is essential for ciliogenesis in normoxia. EMBO Rep. 2014;15:77–85.PubMedCrossRef
146.
Sun H, Li XB, Meng Y, Fan L, Li M, Fang J. TRAF6 upregulates expression of HIF-1alpha and promotes tumor angiogenesis. Cancer Res. 2013;73:4950–9.PubMedCrossRef
147.
Park CV, Ivanova IG, Kenneth NS. XIAP upregulates expression of HIF target genes by targeting HIF1alpha for Lys63-linked polyubiquitination. Nucleic Acids Res. 2017;45:9336–47.PubMedPubMedCentralCrossRef
148.
Shim H, Dolde C, Lewis BC, Wu CS, Dang G, Jungmann RA, Dalla-Favera R, Dang CV. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci U S A. 1997;94:6658–63.PubMedPubMedCentralCrossRef
149.
Lee S, Kim W, Ko C, Ryu WS. Hepatitis B virus X protein enhances Myc stability by inhibiting SCF(Skp2) ubiquitin E3 ligase-mediated Myc ubiquitination and contributes to oncogenesis. Oncogene. 2016;35:1857–67.PubMedCrossRef
150.
The MULE/HUWE1 E3 ubiquitin ligase is a tumor suppressor. Cancer Discov. 2013;3:OF32.
151.
Koch HB, Zhang R, Verdoodt B, Bailey A, Zhang CD, Yates JR 3rd, Menssen A, Hermeking H. Large-scale identification of c-MYC-associated proteins using a combined TAP/MudPIT approach. Cell Cycle. 2007;6:205–17.PubMedCrossRef
152.
Choi SH, Wright JB, Gerber SA, Cole MD. Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells. Genes Dev. 2010;24:1236–41.PubMedPubMedCentralCrossRef
153.
Hakem A, Bohgaki M, Lemmers B, Tai E, Salmena L, Matysiak-Zablocki E, Jung YS, Karaskova J, Kaustov L, Duan SL, et al. Role of Pirh2 in mediating the regulation of p53 and c-Myc. PLoS Genet. 2011;7.
154.
Paul I, Ahmed SF, Bhowmik A, Deb S, Ghosh MK. The ubiquitin ligase CHIP regulates c-Myc stability and transcriptional activity. Oncogene. 2013;32:1284–95.PubMedCrossRef
155.
Fang XG, Zhou WC, Wu QL, Huang Z, Shi Y, Yang KL, Chen C, Xie Q, Mack SC, Wang XX, et al. Deubiquitinase USP13 maintains glioblastoma stem cells by antagonizing FBXL14-mediated Myc ubiquitination. J Exp Med. 2017;214:245–67.PubMedPubMedCentralCrossRef
156.
Luo LY, Tang HL, Ling L, Li N, Jia XT, Zhang ZJ, Wang XR, Shi LJ, Yin J, Qiu N, et al. LINC01638 lncRNA activates MTDH-Twist1 signaling by preventing SPOP-mediated c-Myc degradation in triple-negative breast cancer. Oncogene. 2018;37:6166–79.PubMedCrossRef
157.
Nicklas S, Hillje AL, Okawa S, Rudolph IM, Collmann FM, van Wuellen T, del Sol A, Schwamborn JC. A complex of the ubiquitin ligase TRIM32 and the deubiquitinase USP7 balances the level of c-Myc ubiquitination and thereby determines neural stem cell fate specification. Cell Death Differ. 2019;26:728–40.PubMedCrossRef
158.
Chen J, Li WJ, Cui K, Ji KY, Xu SX, Xu Y. Artemisitene suppresses tumorigenesis by inducing DNA damage through deregulating c-Myc-topoisomerase pathway. Oncogene. 2018;37:5079–87.PubMedCrossRef
159.
Wang SQ, Wang N, Zheng YF, Yang BW, Liu PX, Zhang FX, Li M, Song JX, Chang X, Wang ZY. Caveolin-1 inhibits breast cancer stem cells via c-Myc-mediated metabolic reprogramming. Cell Death Dis. 2020;11.
160.
Gonzalez-Pecchi V, Kwan AK, Doyle S, Ivanov AA, Du Y, Fu H. NSD3S stabilizes MYC through hindering its interaction with FBXW7. J Mol Cell Biol. 2020;12:438–47.PubMedCrossRef
161.
Sriratanasak N, Petsri K, Laobuthee A, Wattanathana W, Vinayanuwattikun C, Luanpitpong S, Chanvorachote P. Novel c-Myc-targeting compound N, N-Bis (5-Ethyl-2-Hydroxybenzyl) methylamine for mediated c-Myc ubiquitin-proteasomal degradation in lung cancer cells. Mol Pharmacol. 2020;98:130–42.PubMedCrossRef
162.
Fiore D, Piscopo C, Proto MC, Vasaturo M, Dal Piaz F, Fusco BM, Pagano C, Laezza C, Bifulco M, Gazzerro P. N6-Isopentenyladenosine inhibits colorectal cancer and improves sensitivity to 5-fluorouracil targeting FBXW7 tumor suppressor. Cancers. 2019;11.
163.
Hu Y, Yu K, Wang G, Zhang D, Shi C, Ding Y, Hong D, Zhang D, He H, Sun L, et al. Lanatoside C inhibits cell proliferation and induces apoptosis through attenuating Wnt/β-catenin/c-Myc signaling pathway in human gastric cancer cell. Biochem Pharmacol. 2018;150:280–92.PubMedCrossRef
164.
Morel M, Shah KN, Long WW. The F-box protein FBXL16 up-regulates the stability of C-MYC oncoprotein by antagonizing the activity of the F-box protein FBW7. J Biol Chem. 2020;295:7970–80.PubMedCrossRefPubMedCentral
165.
Mao CG, Zhou XC, Jiang YD, Wan LJ, Tao ZZ, Guo J. The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein. Cancer Cell Int. 2020;20.
166.
Ma S, Lu CC, Yang LY, Wang JJ, Wang BS, Cai HQ, Hao JJ, Xu X, Cai Y, Zhang Y, Wang MR. ANXA2 promotes esophageal cancer progression by activating MYC-HIF1A-VEGF axis. J Exp Clin Cancer Res. 2018;37.
167.
He J, Li FZ, Zhou Y, Hou XY, Liu SS, Li XC, Zhang YW, Jing XQ, Yang LP. LncRNA XLOC_006390 promotes pancreatic carcinogenesis and glutamate metabolism by stabilizing c-Myc. Cancer Lett. 2020;469:419–28.PubMedCrossRef
168.
Tang JY, Yan TT, Bao YJ, Shen CQ, Yu CY, Zhu XQ, Tian XL, Guo FF, Liang Q, Liu Q, et al. LncRNA GLCC1 promotes colorectal carcinogenesis and glucose metabolism by stabilizing c-Myc. Nat Commun. 2019;10.
169.
Cepeda D, Ng HF, Sharifi HR, Mahmoudi S, Cerrato VS, Fredlund E, Magnusson K, Nilsson H, Malyukova A, Rantala J, et al. CDK-mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer. Embo Mol Med. 2013;5:1067–86.PubMedCrossRef
170.
Popov N, Schulein C, Jaenicke LA, Eilers M. Ubiquitylation of the amino terminus of Myc by SCF beta-TrCP antagonizes SCFFbw7-mediated turnover. Nat Cell Biol. 2010;12:973–81.PubMedCrossRef
171.
Sun XX, He X, Yin L, Sears R, Dai MS. The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc. Cancer Res. 2015;75.
172.
Pan J, Deng Q, Jiang C, Wang X, Niu T, Li H, Chen T, Jin J, Pan W, Cai X, et al. USP37 directly deubiquitinates and stabilizes c-Myc in lung cancer. Oncogene. 2015;34:3957–67.PubMedCrossRef
173.
Zhang WL, Liu ZK, Wang JM, Tian QB. Knockdown of USP28 enhances the radiosensitivity of esophageal cancer cells via the c-Myc/hypoxia-inducible factor-1 alpha pathway. J Cell Biochem. 2019;120:201–12.CrossRef
174.
Kim D, Hong A, Park HI, Shin WH, Yoo L, Jeon SJ, Chung KC. Deubiquitinating enzyme USP22 positively regulates c-Myc stability and tumorigenic activity in mammalian and breast cancer cells. J Cell Physiol. 2017;232:3664–76.PubMedCrossRef
175.
Li X, Wu LM, Zopp M, Kopelov S, Du W. p53-TP53-induced glycolysis regulator mediated glycolytic suppression attenuates DNA damage and genomic instability in fanconi anemia hematopoietic stem cells. Stem Cells. 2019;37:937–47.PubMedPubMedCentralCrossRef
176.
177.
178.
Bang S, Kaur S, Kurokawa M. Regulation of the p53 family proteins by the ubiquitin proteasomal pathway. Int J Mol Sci. 2020:21.
179.
Allton K, Jain AK, Herz HM, Tsai WW, Jung SY, Qin J, Bergmann A, Johnson RL, Barton MC. Trim24 targets endogenous p53 for degradation. Proc Natl Acad Sci U S A. 2009;106:11612–6.PubMedPubMedCentralCrossRef
180.
Banks D, Wu M, Higa LA, Gavrilova N, Quan JM, Ye T, Kobayashi R, Sun H, Zhang H. L2DTL/CDT2 and PCNA interact with p53 and regulate p53 polyubiquitination and protein stability through MDM2 and CUL4A/DDB1 complexes. Cell Cycle. 2006;5:1719–29.PubMedCrossRef
181.
Luo K, Ehrlich E, Xiao ZX, Zhang WY, Ketner G, Yu XF. Adenovirus E4orF6 assembles with Cullin5-ElonginB-ElonginC E3 ubiquitin ligase through an HIV/SIV Vif-like BC-box to regulate p53. FASEB J. 2007;21:1742–50.PubMedCrossRef
182.
Luo Z, Ye X, Shou F, Cheng Y, Li F, Wang G. RNF115-mediated ubiquitination of p53 regulates lung adenocarcinoma proliferation. Biochem Biophys Res Commun. 2020.
183.
Han YD, Tan Y, Zhao YY, Zhang YC, He XJ, Yu L, Jiang HP, Lu HJ, Tian HY. TRIM23 overexpression is a poor prognostic factor and contributes to carcinogenesis in colorectal cancer. J Cell Mol Med. 2020;24:5491–500.PubMedPubMedCentralCrossRef
184.
Zhang YL, Cui NN, Zheng G. Ubiquitination of P53 by E3 ligase MKRN2 promotes melanoma cell proliferation. Oncol Lett. 2020;19:1975–84.PubMedPubMedCentral
185.
Weber JD, Taylor LJ, Roussel MF, Sherr CJ, Bar-Sagi D. Nucleolar Arf sequesters Mdm2 and activates p53. Nat Cell Biol. 1999;1:20–6.PubMedCrossRef
186.
Zhang WC, Gong J, Yang H, Wan LM, Peng YM, Wang XL, Sun J, Li F, Geng YQ, Li DY, et al. The mitochondrial protein MAVS stabilizes p53 to suppress tumorigenesis. Cell Rep. 2020;30:725.PubMedCrossRef
187.
Li XY, Guo MQ, Cai L, Du TT, Liu Y, Ding HF, Wang HB, Zhang JR, Chen XG, Yan CH. Competitive ubiquitination activates the tumor suppressor p53. Cell Death Differ. 2020;27:1807–18.PubMedCrossRef
188.
Hu YN, Yu J, Wang Q, Zhang L, Chen XY, Cao Y, Zhao JP, Xu YJ, Jiang DS, Wang Y, Xiong WN. Tartrate-resistant acid phosphatase 5/ACP5 interacts with p53 to control the expression of SMAD3 in lung adenocarcinoma. Mol Ther Oncol. 2020;16:272–88.CrossRef
189.
Lim KH, Park JJ, Gu BH, Kim JO, Park SG, Baek KH. HAUSP-nucleolin interaction is regulated by p53-Mdm2 complex in response to DNA damage response. Sci Rep. 2015;5.
190.
191.
Liu WT, Huang KY, Lu MC, Huang HL, Chen CY, Cheng YL, Yu HC, Liu SQ, Lai NS, Huang HB. TGF-beta upregulates the translation of USP15 via the PI3K/AKT pathway to promote p53 stability. Oncogene. 2017;36:2715–23.PubMedCrossRef
192.
Pu Q, Lv YR, Dong K, Geng WW, Gao HD. Tumor suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells. BMC Cancer. 2020;20:583.PubMedPubMedCentralCrossRef
193.
Piao SD, Pei HZ, Huang B, Baek SH. Ovarian tumor domain-containing protein 1 deubiquitinates and stabilizes p53. Cell Signal. 2017;33:22–9.PubMedCrossRef
194.
Luo JD, Lu ZH, Lu XJ, Chen L, Cao JP, Zhang SY, Ling Y, Zhou XF. OTUD5 regulates p53 stability by deubiquitinating p53. PLoS One. 2013;8.
195.
196.
Liu J, Chung HJ, Vogt M, Jin Y, Malide D, He L, Dundr M, Levens D. JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress. EMBO J. 2011;30:846–58.PubMedPubMedCentralCrossRef
197.
Hock AK, Vigneron AM, Carter S, Ludwig RL, Vousden KH. Regulation of p53 stability and function by the deubiquitinating enzyme USP42. EMBO J. 2011;30:4921–30.PubMedPubMedCentralCrossRef
198.
Ke JY, Dai CJ, Wu WL, Gao JH, Xia AJ, Liu GP, Lv KS, Wu CL. USP11 regulates p53 stability by deubiquitinating p53. J Zhejiang Univ Sci B. 2014;15:1032–8.PubMedPubMedCentralCrossRef
199.
Li M, Chen D, Shiloh A, Luo J, Nikolaev AY, Qin J, Gu W. Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature. 2002;416:648–53.PubMedCrossRef
200.
Sheng Y, Saridakis V, Sarkari F, Duan S, Wu T, Arrowsmith CH, Frappier L. Molecular recognition of p53 and MDM2 by USP7/HAUSP. Nat Struct Mol Biol. 2006;13:285–91.PubMedCrossRef
201.
Sarkari F, La Delfa A, Arrowsmith CH, Frappier L, Sheng Y, Saridakis V. Further insight into substrate recognition by USP7: structural and biochemical analysis of the HdmX and Hdm2 interactions with USP7. J Mol Biol. 2010;402:825–37.PubMedCrossRef
202.
An T, Gong Y, Li X, Kong L, Ma P, Gong L, Zhu H, Yu C, Liu J, Zhou H, et al. USP7 inhibitor P5091 inhibits Wnt signaling and colorectal tumor growth. Biochem Pharmacol. 2017;131:29–39.PubMedCrossRef
203.
Xia X, Liao Y, Huang C, Liu Y, He J, Shao Z, Jiang L, Dou QP, Liu J, Huang H. Deubiquitination and stabilization of estrogen receptor alpha by ubiquitin-specific protease 7 promotes breast tumorigenesis. Cancer Lett. 2019;465:118–28.PubMedCrossRef
204.
Fan YH, Cheng J, Vasudevan SA, Dou J, Zhang H, Patel RH, Ma IT, Rojas Y, Zhao Y, Yu Y, et al. USP7 inhibitor P22077 inhibits neuroblastoma growth via inducing p53-mediated apoptosis. Cell Death Dis. 2013;4:e867.PubMedPubMedCentralCrossRef
205.
Masuya D, Huang C, Liu D, Nakashima T, Yokomise H, Ueno M, Nakashima N, Sumitomo S. The HAUSP gene plays an important role in non-small cell lung carcinogenesis through p53-dependent pathways. J Pathol. 2006;208:724–32.PubMedCrossRef
206.
207.
Yang YL, Ludwig RL, Jensen JP, Pierre SA, Medaglia MV, Davydov IV, Safiran YJ, Oberoi P, Kenten JH, Phillips AC, et al. Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell. 2005;7:547–59.PubMedCrossRef
208.
Jiang J, Tam LM, Wang PC, Wang YS. Arsenite targets the RING finger domain of Rbx1 E3 ubiquitin ligase to inhibit proteasome-mediated degradation of Nrf2. Chem Res Toxicol. 2018;31:380–7.PubMedPubMedCentralCrossRef
209.
Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, Sou YS, Ueno I, Sakamoto A, Tong KI, et al. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol. 2010;12:213–U217.PubMedCrossRef
210.
Wan ZH, Jiang TY, Shi YY, Pan YF, Lin YK, Ma YH, Yang C, Feng XF, Huang LF, Kong XN, et al. RPB5-mediating protein promotes cholangiocarcinoma tumorigenesis and drug resistance by competing with NRF2 for KEAP1 binding. Hepatology. 2020;71:2005–22.PubMedCrossRef
211.
Wang Q, Ma J, Lu Y, Zhang S, Huang J, Chen J, Bei JX, Yang K, Wu G, Huang K, et al. CDK20 interacts with KEAP1 to activate NRF2 and promotes radiochemoresistance in lung cancer cells. Oncogene. 2017;36:5321–30.PubMedCrossRef
212.
Liu YF, Tao SS, Liao LJ, Li Y, Li HC, Li ZH, Lin LL, Wan XC, Yang XL, Chen L. TRIM25 promotes the cell survival and growth of hepatocellular carcinoma through targeting Keap1-Nrf2 pathway. Nat Commun. 2020;11.
213.
Xu PF, Jiang LP, Yang Y, Wu MG, Liu BY, Shi YL, Shen QS, Jiang XL, He YM, Cheng DT, et al. PAQR4 promotes chemoresistance in non-small cell lung cancer through inhibiting Nrf2 protein degradation. Theranostics. 2020;10:3767–78.PubMedPubMedCentralCrossRef
214.
Yu YP, Cai LC, Wang XY, Cheng SY, Zhang M, Jian WG, Wang TD, Yang JK, Yang KB, Zhang C. BMP8A promotes survival and drug resistance via Nrf2/TRIM24 signaling pathway in clear cell renal cell carcinoma. Cancer Sci. 2020;111:1555–66.PubMedPubMedCentralCrossRef
215.
Lo JY, Spatola BN, Curran SP. WDR23 regulates NRF2 independently of KEAP1. Plos Genet. 2017;13.
216.
Cuadrado A. Structural and functional characterization of Nrf2 degradation by glycogen synthase kinase 3/beta-TrCP. Free Radic Biol Med. 2015;88:147–57.PubMedCrossRef
217.
Wu TD, Zhao F, Gao BX, Tan C, Yagishita N, Nakajima T, Wong PK, Chapman E, Fang DY, Zhang DD. Hrd1 suppresses Nrf2-mediated cellular protection during liver cirrhosis. Genes Dev. 2014;28:708–22.PubMedPubMedCentralCrossRef
218.
Zhang Q, Zhang ZY, Du H, Li SZ, Tu R, Jia YF, Zheng Z, Song XM, Du RL, Zhang XD. DUB3 deubiquitinates and stabilizes NRF2 in chemotherapy resistance of colorectal cancer. Cell Death Differ. 2019;26:2300–13.PubMedCrossRefPubMedCentral
219.
Sun Y, He W, Luo M, Zhou Y, Chang G, Ren W, Wu K, Li X, Shen J, Zhao X, Hu Y. SREBP1 regulates tumorigenesis and prognosis of pancreatic cancer through targeting lipid metabolism. Tumour Biol. 2015;36:4133–41.PubMedCrossRef
220.
Bakan I, Laplante M. Connecting mTORC1 signaling to SREBP-1 activation. Curr Opin Lipidol. 2012;23:226–34.PubMedCrossRef
221.
Zhao XP, Feng DR, Wang Q, Abdulla A, Xie XJ, Zhou J, Sun Y, Yang ES, Liu LP, Vaitheesvaran B, et al. Regulation of lipogenesis by cyclin-dependent kinase 8-mediated control of SREBP-1. J Clin Investig. 2012;122:2417–27.PubMedCrossRefPubMedCentral
222.
Tu KS, Zheng X, Yin GZ, Zan XF, Yao YM, Liu QG. Evaluation of Fbxw7 expression and its correlation with expression of SREBP-1 in a mouse model of NAFLD. Mol Med Rep. 2012;6:525–30.PubMedCrossRef
223.
Walker AK, Yang FJ, Jiang KR, Ji JY, Watts JL, Purushotham A, Boss O, Hirsch ML, Ribich S, Smith JJ, et al. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev. 2010;24:1403–17.PubMedPubMedCentralCrossRef
224.
Lee JP, Brauweiler A, Rudolph M, Hooper JE, Drabkin HA, Gemmill RM. The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and protein biosynthetic pathways. Mol Cancer Res. 2010;8:93–106.PubMedPubMedCentralCrossRef
225.
Han SH, Korm S, Han YG, Choi SY, Kim SH, Chung HJ, Park K, Kim JY, Myung K, Lee JY, et al. GCA links TRAF6-ULK1-dependent autophagy activation in resistant chronic myeloid leukemia. Autophagy. 2019;15:2076–90.PubMedPubMedCentralCrossRef
226.
Nazio F, Strappazzon F, Antonioli M, Bielli P, Cianfanelli V, Bordi M, Gretzmeier C, Dengjel J, Piacentini M, Fimia GM, Cecconi F. mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat Cell Biol. 2013;15:406.PubMedCrossRef
227.
Chauhan S, Kumar S, Jain A, Ponpuak M, Mudd MH, Kimura T, Choi SW, Peters R, Mandell M, Bruun JA, et al. TRIMs and galectins globally cooperate and TRIM16 and galectin-3 co-direct autophagy in endomembrane damage homeostasis. Dev Cell. 2016;39:13–27.PubMedPubMedCentralCrossRef
228.
Di Rienzo M, Antonioli M, Fusco C, Liu Y, Mari M, Orhon I, Refolo G, Germani F, Corazzari M, Romagnoli A, et al. Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains. Sci Adv. 2019;5.
229.
Raimondi M, Cesselli D, Di Loreto C, La Marra F, Schneider C, Demarchi F. USP1 (ubiquitin specific peptidase 1) targets ULK1 and regulates its cellular compartmentalization and autophagy. Autophagy. 2019;15:613–30.PubMedCrossRef
230.
Thayer JA, Awad O, Hegdekar N, Sarkar C, Tesfay H, Burt C, Zeng X, Feldman RA, Lipinski MM. The PARK10 gene USP24 is a negative regulator of autophagy and ULK1 protein stability. Autophagy. 2020;16:140–53.PubMedCrossRef
231.
232.
233.
Kim JH, Seo D, Kim SJ, Choi DW, Park JS, Ha J, Choi J, Lee JH, Jung SM, Seo KW, et al. The deubiquitinating enzyme USP20 stabilizes ULK1 and promotes autophagy initiation. EMBO Rep. 2018;19.
234.
Chang YY, Juhasz G, Goraksha-Hicks P, Arsham AM, Mallin DR, Muller LK, Neufeld TP. Nutrient-dependent regulation of autophagy through the target of rapamycin pathway. Biochem Soc Trans. 2009;37:232–6.PubMedCrossRef
235.
Shi CS, Kehrl JH. TRAF6 and A20 regulate lysine 63-linked ubiquitination of beclin-1 to control TLR4-induced autophagy. Sci Signal. 2010;3.
236.
Xia PY, Wang S, Du Y, Zhao ZN, Shi L, Sun L, Huang GL, Ye BQ, Li C, Dai ZH, et al. WASH inhibits autophagy through suppression of Beclin 1 ubiquitination. EMBO J. 2013;32:2685–96.PubMedPubMedCentralCrossRef
237.
Fusco C, Mandriani B, Di Rienzo M, Micale L, Malerba N, Cocciadiferro D, Sjottem E, Augello B, Squeo GM, Pellico MT, et al. TRIM50 regulates Beclin 1 proautophagic activity. Biochim Biophys Acta Mol Cell Res. 2018;1865:908–19.PubMedCrossRef
238.
Xu DC, Shan B, Sun HW, Xiao J, Zhu KZ, Xie XX, Li XY, Liang W, Lu XJ, Qian LH, Yuan JY. USP14 regulates autophagy by suppressing K63 ubiquitination of Beclin 1. Genes Dev. 2016;30:1718–30.PubMedPubMedCentralCrossRef
239.
Platta HW, Abrahamsen H, Thoresen SB, Stenmark H. Nedd4-dependent lysine-11-linked polyubiquitination of the tumour suppressor Beclin 1. Biochem J. 2012;441:399–406.PubMedCrossRef
240.
Xu CF, Feng K, Zhao XN, Huang SQ, Cheng YJ, Qian L, Wang YN, Sun HX, Jin M, Chuang TH, Zhang YY. Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination. Autophagy. 2014;10:2239–50.PubMedCrossRef
241.
Liu JL, Xia HG, Kim M, Xu LH, Li Y, Zhang LH, Cai Y, Norberg HV, Zhang T, Furuya T, et al. Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell. 2011;147:223–34.PubMedPubMedCentralCrossRef
242.
Jin SH, Tian S, Chen YM, Zhang CX, Xie WH, Xia XJ, Cui J, Wang RF. USP19 modulates autophagy and antiviral immune responses by deubiquitinating beclin-1. EMBO J. 2016;35:866–80.PubMedPubMedCentralCrossRef
243.
Ashkenazi A, Bento CF, Ricketts T, Vicinanza M, Siddiqi F, Pavel M, Squitieri F, Hardenberg MC, Imarisio S, Menzies FM, Rubinsztein DC. Polyglutamine tracts regulate beclin 1-dependent autophagy. Nature. 2017;545:108.PubMedPubMedCentralCrossRef
244.
Xiao J, Zhang T, Xu DC, Wang HB, Cai Y, Jin TJ, Liu M, Jin MZ, Wu KJ, Yuan JY. FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation. Genes Dev. 2015;29:184–96.PubMedPubMedCentralCrossRef
245.
Zhang T, Dong KY, Liang W, Xu DC, Xia HG, Geng JF, Najafov A, Liu M, Li YX, Han XR, et al. G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L. Elife. 2015;4.
246.
247.
Wan W, You ZY, Zhou L, Xu YF, Peng C, Zhou TH, Yi C, Shi Y, Liu W. mTORC1-regulated and HUWE1-mediated WIPI2 degradation controls autophagy flux. Mol Cell. 2018;72:303.PubMedCrossRef
248.
Kuang E, Okumura CYM, Sheffy-Levin S, Varsano T, Shu VCW, Qi JF, Niesman IR, Yang HJ, Lopez-Otin C, Yang WY, et al. Regulation of ATG4B stability by RNF5 limits basal levels of autophagy and influences susceptibility to bacterial infection (vol 8, e1003007, 2012). PLoS Genet. 2020;16.
249.
Liu CH, Zhang Y, She XL, Fan L, Li PY, Feng JB, Fu HJ, Liu Q, Liu Q, Zhao CH, et al. A cytoplasmic long noncoding RNA LINC00470 as a new AKT activator to mediate glioblastoma cell autophagy. J Hematol Oncol. 2018;11.
250.
Lee HJ, Li CF, Ruan D, He J, Montal ED, Lorenz S, Girnun GD, Chan CH. Non-proteolytic ubiquitination of hexokinase 2 by HectH9 controls tumor metabolism and cancer stem cell expansion. Nat Commun. 2019;10.
251.
Jiao L, Zhang HL, Li DD, Yang KL, Tang J, Li X, Ji J, Yu Y, Wu RY, Ravichandran S, et al. Regulation of glycolytic metabolism by autophagy in liver cancer involves selective autophagic degradation of HK2 (hexokinase 2). Autophagy. 2018;14:671–84.PubMedCrossRef
252.
Huang MW, Xiong H, Luo DL, Xu BR, Liu HL. CSN5 upregulates glycolysis to promote hepatocellular carcinoma metastasis via stabilizing the HK2 protein. Exp Cell Res. 2020;388.
253.
Okatsu K, Iemura S, Koyano F, Go E, Kimura M, Natsume T, Tanaka K, Matsuda N. Mitochondrial hexokinase HKI is a novel substrate of the Parkin ubiquitin ligase. Biochem Biophys Res Commun. 2012;428:197–202.PubMedCrossRef
254.
Feng YL, Zhang Y, Cai Y, Liu RJ, Lu ML, Li TZM, Fu Y, Guo M, Huang HC, Ou YF, Chen YH. A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma. Cell Death Dis. 2020;11.
255.
Lee JH, Liu R, Li J, Zhang CB, Wang YG, Cai QS, Qian X, Xia Y, Zheng YH, Piao YJ, et al. Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis. Nat Commun. 2017;8.
256.
Shang Y, He J, Wang Y, Feng Q, Zhang Y, Guo J, Li J, Li S, Wang Y, Yan G, et al. CHIP/Stub1 regulates the Warburg effect by promoting degradation of PKM2 in ovarian carcinoma. Oncogene. 2017;36:4191–200.PubMedCrossRef
257.
Yuan P, Zhou YY, Wang R, Chen SY, Wang QQ, Xu ZJ, Liu Y, Yang HL. TRIM58 interacts with pyruvate kinase M2 to inhibit tumorigenicity in human osteosarcoma cells. Biomed Res Int. 2020;2020.
258.
Liu K, Li FZ, Han HC, Chen Y, Mao ZB, Luo JY, Zhao YM, Zheng B, Gu W, Zhao WH. Parkin regulates the activity of pyruvate kinase M2. J Biol Chem. 2016;291:10307–17.PubMedPubMedCentralCrossRef
259.
Choi HS, Pei CZ, Park JH, Kim SY, Song SY, Shin GJ, Baek KH. Protein stability of pyruvate kinase Isozyme M2 is mediated by HAUSP. Cancers (Basel). 2020;12.
260.
Kim SR, Kim JO, Lim KH, Yun JH, Han I, Baek KH. Regulation of pyruvate kinase isozyme M2 is mediated by the ubiquitin-specific protease 20. Int J Oncol. 2015;46:2116–24.PubMedCrossRef
261.
Wang Y, Ha SW, Zhang T, Kho DH, Raz A, Xie Y. Polyubiquitylation of AMF requires cooperation between the gp78 and TRIM25 ubiquitin ligases. Oncotarget. 2014;5:2044–51.PubMedCrossRef
262.
Deng XQ, Yi X, Deng JY, Zou YQ, Wang SS, Shan WH, Liu P, Zhang ZB, Chen LF, Hao L. ROCK2 promotes osteosarcoma growth and metastasis by modifying PFKFB3 ubiquitination and degradation. Exp Cell Res. 2019;385.
263.
Tudzarova S, Colombo SL, Stoeber K, Carcamo S, Williams GH, Moncada S. Two ubiquitin ligases, APC/C-Cdh1 and SKP1-CUL1-F (SCF)-beta-TrCP, sequentially regulate glycolysis during the cell cycle. Proc Natl Acad Sci U S A. 2011;108:5278–83.PubMedPubMedCentralCrossRef
264.
Colombo SL, Palacios-Callender M, Frakich N, Carcamo S, Kovacs I, Tudzarova S, Moncada S. Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells. Proc Natl Acad Sci U S A. 2011;108:21069–74.PubMedPubMedCentralCrossRef
265.
Cai Q, Wang SH, Jin LY, Weng MZ, Zhou D, Wang JD, Tang ZH, Quan ZW. Long non-coding RNA GBCDRlnc1 induces chemoresistance of gallbladder cancer cells by activating autophagy. Mol Cancer. 2019;18.
266.
Yu T, Zhao YJ, Hu ZX, Li J, Chu DD, Zhang JW, Li Z, Chen B, Zhang X, Pan HY, et al. MetaLnc9 facilitates lung cancer metastasis via a PGK1-activated AKT/mTOR pathway. Cancer Res. 2017;77:5782–94.PubMedCrossRef
267.
Mikawa T, Maruyama T, Okamoto K, Nakagama H, Lleonart ME, Tsusaka T, Hori K, Murakami I, Izumi T, Takaori-Kondo A, et al. Senescence-inducing stress promotes proteolysis of phosphoglycerate mutase via ubiquitin ligase Mdm2. J Cell Biol. 2014;204:729–45.PubMedPubMedCentralCrossRef
268.
Yoshino S, Hara T, Nakaoka HJ, Kanamori A, Murakami Y, Seiki M, Sakamoto T. The ERK signaling target RNF126 regulates anoikis resistance in cancer cells by changing the mitochondrial metabolic flux. Cell Discov. 2016;2.
269.
Peng MX, Yang D, Hou YX, Liu SQ, Zhao MJ, Qin YL, Chen R, Teng Y, Liu MR. Intracellular citrate accumulation by oxidized ATM-mediated metabolism reprogramming via PFKP and CS enhances hypoxic breast cancer cell invasion and metastasis. Cell Death Dis. 2019;10.
270.
Sun RC, Denko NC. Hypoxic regulation of glutamine metabolism through HIF1 and SIAH2 supports lipid synthesis that is necessary for tumor growth. Cell Metab. 2014;19:285–92.PubMedPubMedCentralCrossRef
271.
Han C. Amplification of Usp13 drives ovarian cancer metabolism. Clin Cancer Res. 2019;25:90.CrossRef
272.
Wang M, Hu J, Yan LL, Yang YP, He M, Wu M, Li Q, Gong W, Yang Y, Wang Y, et al. High glucose-induced ubiquitination of G6PD leads to the injury of podocytes. FASEB J. 2019;33:6296–310.PubMedCrossRef
273.
Yu F, White SB, Zhao Q, Lee FS. HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proc Natl Acad Sci U S A. 2001;98:9630–5.PubMedPubMedCentralCrossRef
274.
Jin X, Pan Y, Wang L, Zhang L, Ravichandran R, Potts PR, Jiang J, Wu H, Huang H. MAGE-TRIM28 complex promotes the Warburg effect and hepatocellular carcinoma progression by targeting FBP1 for degradation. Oncogenesis. 2017;6:e312.PubMedPubMedCentralCrossRef
275.
Jiang WQ, Wang SW, Xiao MT, Lin Y, Zhou LS, Lei QY, Xiong Y, Guan KL, Zhao SM. Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Mol Cell. 2011;43:33–44.PubMedPubMedCentralCrossRef
276.
Fernandes R, Carvalho A, Kumagai A, Seica R, Hosoya KI, Terasaki T, Murta J, Pereira P, Faro C. Downregulation of retinal GLUT1 in diabetes by ubiquitinylation. Mol Vis. 2004;10:618–28.PubMed
277.
Cheng A, Zhang M, Gentry MS, Worby CA, Dixon JE, Saltiel AR. A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori’s disease. Genes Dev. 2007;21:2399–409.PubMedPubMedCentralCrossRef
278.
Zhang C, Liu J, Zhao YH, Yue XT, Wu H, Li J, Shen ZY, Haffty B, Hu WW, Feng ZH. Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression. Cancer Res. 2017;77.
279.
Gu L, Zhu Y, Lin X, Lu B, Zhou X, Zhou F, Zhao Q, Prochownik EV, Li Y. The IKKbeta-USP30-ACLY axis controls Lipogenesis and tumorigenesis. Hepatology. 2020.
280.
Qi L, Heredia JE, Altarejos JY, Screaton R, Goebel N, Niessen S, MacLeod IX, Liew CW, Kulkarni RN, Bain J, et al. TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism. Science. 2006;312:1763–6.PubMedCrossRef
281.
Ma J, Yan RL, Zu X, Cheng JM, Rao K, Liao DF, Cao DL. Aldo-keto reductase family 1 B10 affects fatty acid synthesis by regulating the stability of acetyl-CoA carboxylase-alpha in breast cancer cells. J Biol Chem. 2008;283:3418–23.PubMedCrossRef
282.
Yu JX, Deng R, Zhu HH, Zhang SS, Zhu CH, Montminy M, Davis R, Feng GS. Modulation of fatty acid synthase degradation by concerted action of p38 MAP kinase, E3 ligase COP1, and SH2-tyrosine phosphatase Shp2. J Biol Chem. 2013;288:3823–30.PubMedCrossRef
283.
Gang XK, Xuan LL, Zhao X, Lv Y, Li F, Wang Y, Wang GX. Speckle-type POZ protein suppresses lipid accumulation and prostate cancer growth by stabilizing fatty acid synthase. Prostate. 2019;79:864–71.PubMedCrossRef
284.
Calvisi DF, Wang CM, Ho C, Ladu S, Lee SA, Mattu S, Destefanis G, Delogu S, Zimmermann A, Ericsson J, et al. Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma. Gastroenterology. 2011;140:1071–U1542.PubMedCrossRef
285.
Graner E, Tang D, Rossi S, Baron A, Migita T, Weinstein LJ, Lechpammer M, Huesken D, Zimmermann J, Signoretti S, Loda M. The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer. Cancer Cell. 2004;5:253–61.PubMedCrossRef
286.
Menzies SA, Volkmar N, van den Boomen DJ, Timms RT, Dickson AS, Nathan JA, Lehner PJ. The sterol-responsive RNF145 E3 ubiquitin ligase mediates the degradation of HMG-CoA reductase together with gp78 and Hrd1. Elife. 2018;7.
287.
Jiang LY, Jiang W, Tian N, Xiong YN, Liu J, Wei J, Wu KY, Luo J, Shi XJ, Song BL. Ring finger protein 145 (RNF145) is a ubiquitin ligase for sterol-induced degradation of HMG-CoA reductase. J Biol Chem. 2018;293:4047–55.PubMedPubMedCentralCrossRef
288.
Loregger A, Raaben M, Tan J, Scheij S, Moeton M, van den Berg M, Gelberg-Etel H, Stickel E, Roitelman J, Brummelkamp T, Zelcer N. Haploid mammalian genetic screen identifies UBXD8 as a key determinant of HMGCR degradation and cholesterol biosynthesis. Arterioscler Thromb Vasc Biol. 2017;37:2064.PubMedPubMedCentralCrossRef
289.
Hwang S, Nguyen AD, Jo Y, Engelking LJ, Brugarolas J, DeBose-Boyd RA. Hypoxia-inducible factor 1alpha activates insulin-induced gene 2 (Insig-2) transcription for degradation of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase in the liver. J Biol Chem. 2017;292:9382–93.PubMedPubMedCentralCrossRef
290.
Gelsomino G, Corsetto PA, Campia I, Montorfano G, Kopecka J, Castella B, Gazzano E, Ghigo D, Rizzo AM, Riganti C. Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition. Mol Cancer. 2013;12.
291.
Foresti O, Ruggiano A, Hannibal-Bach HK, Ejsing CS, Carvalho P. Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4. Elife. 2013;2:e00953.PubMedPubMedCentralCrossRef
292.
Zelcer N, Hong C, Boyadjian R, Tontonoz P. LXR regulates cholesterol uptake through idol-dependent ubiquitination of the LDL receptor. Science. 2009;325:100–4.PubMedPubMedCentralCrossRef
293.
Lee DE, Yoo JE, Kim J, Kim S, Kim S, Lee H, Cheong HS. NEDD4L downregulates autophagy and cell growth by modulating ULK1 and a glutamine transporter. Cell Death Dis. 2020;11.
294.
Jeon YJ, Khelifa S, Ratnikov B, Scott DA, Feng YM, Parisi F, Ruller C, Lau E, Kim H, Brill LM, et al. Regulation of glutamine carrier proteins by RNF5 determines breast cancer response to ER stress-inducing chemotherapies. Cancer Cell. 2015;27:354–69.PubMedPubMedCentralCrossRef
295.
Zhao S, Wang JM, Yan J, Zhang DL, Liu BQ, Jiang JY, Li C, Li S, Meng XN, Wang HQ. BAG3 promotes autophagy and glutaminolysis via stabilizing glutaminase. Cell Death Dis. 2019;10.
296.
Zhao JZ, Zhou R, Hui KY, Yang Y, Zhang QY, Ci YL, Shi L, Xu CM, Huang F, Hu Y. Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells. Oncotarget. 2017;8:18832–47.PubMedCrossRef
297.
Liu J, Zhang C, Wu H, Sun XX, Li Y, Huang S, Yue X, Lu SE, Shen Z, Su X, et al. Parkin ubiquitinates phosphoglycerate dehydrogenase to suppress serine synthesis and tumor progression. J Clin Invest. 2020;130:3253–69.PubMedPubMedCentralCrossRef
298.
Anderson DD, Eom JY, Stover PJ. Competition between sumoylation and ubiquitination of serine hydroxymethyltransferase 1 determines its nuclear localization and its accumulation in the nucleus. J Biol Chem. 2012;287:4790–9.PubMedCrossRef
299.
Li Z, Zhang H. Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression. Cell Mol Life Sci. 2016;73:377–92.PubMedCrossRef
300.
Cui D, Xiong X, Shu J, Dai X, Sun Y, Zhao Y. FBXW7 confers radiation survival by targeting p53 for degradation. Cell Rep. 2020;30:497–509 e494.PubMedCrossRef
Metadata
Title
The role of ubiquitination and deubiquitination in cancer metabolism
Authors
Tianshui Sun
Zhuonan Liu
Qing Yang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2020
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-020-01262-x

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