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Experimental Hematology & Oncology
Published in: Experimental Hematology & Oncology 1/2017

Open Access 01-12-2017 | Research

PTEN is a negative regulator of mitotic checkpoint complex during the cell cycle

Authors: Byeong H. Choi, Steve Xie, Wei Dai

Published in: Experimental Hematology & Oncology | Issue 1/2017

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Abstract

Nuclear PTEN plays an important role during mitosis. To understand the molecular basis by which PTEN mediates mitotic progression, we examined whether PTEN regulated the formation of mitotic checkpoint complex (MCC). We observed that arsenic trioxide, a mitotic inducer, stimulated nuclear translocation of PTEN in a time-dependent manner. PTEN physically interacted with Cdc20 and Mad2, two important components of MCC. Arsenic treatment diminished the physical association of PTEN with BubR1 and Bub3 but not with Cdc20 and Mad2. Our further studies revealed that downregulation of PTEN via RNAi enhanced formation of MCC during the cell cycle. Moreover, PTEN silencing induced chromosomal instability. Given the crucial role of PTEN in suppressing tumor development, our study strongly suggests that PTEN also functions to maintain chromosomal stability, partly through suppressing unscheduled formation of MCC.
Literature
1.
Shen ZX, et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood. 1997;89(9):3354–60.PubMed
2.
Chen GQ, et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells. Blood. 1997;89(9):3345–53.PubMed
3.
Zhu J, et al. Arsenic-induced PML targeting onto nuclear bodies: implications for the treatment of acute promyelocytic leukemia. Proc Natl Acad Sci USA. 1997;94(8):3978–83.CrossRefPubMedPubMedCentral
4.
Sankpal UT, et al. Environmental factors in causing human cancers: emphasis on tumorigenesis. Tumour Biol. 2012;33(5):1265–74.CrossRefPubMed
5.
Ng JC, Wang J, Shraim A. A global health problem caused by arsenic from natural sources. Chemosphere. 2003;52(9):1353–9.CrossRefPubMed
6.
Lee L, Bebb G. A case of Bowen’s disease and small-cell lung carcinoma: long-term consequences of chronic arsenic exposure in Chinese traditional medicine. Environ Health Perspect. 2005;113(2):207–10.CrossRefPubMed
7.
8.
Ahlborn GJ, et al. Impact of life stage and duration of exposure on arsenic-induced proliferative lesions and neoplasia in C3H mice. Toxicology. 2009;262(2):106–13.CrossRefPubMedPubMedCentral
9.
Chen YJ, et al. HSP70 colocalizes with PLK1 at the centrosome and disturbs spindle dynamics in cells arrested in mitosis by arsenic trioxide. Arch Toxicol. 2014;88(9):1711–23.CrossRefPubMed
10.
Halicka HD, Smolewski P, Darzynkiewicz Z, Dai W, Traganos F. Arsenic trioxide arrests cells early in mitosis leading to apoptosis. Cell Cycle. 2002;1(3):201–9.CrossRefPubMed
11.
Cai X, et al. Arsenic trioxide-induced mitotic arrest and apoptosis in acute promyelocytic leukemia cells. Leukemia. 2003;17(7):1333–7.CrossRefPubMed
12.
Meister MT, et al. Arsenic trioxide induces Noxa-dependent apoptosis in rhabdomyosarcoma cells and synergizes with antimicrotubule drugs. Cancer Lett. 2016;381(2):287–95.CrossRefPubMed
13.
Zhao Y, Toselli P, Li W. Microtubules as a critical target for arsenic toxicity in lung cells in vitro and in vivo. Int J Environ Res Public Health. 2012;9(2):474–95.CrossRefPubMedPubMedCentral
14.
Duan XF, et al. Synergistic mitosis-arresting effects of arsenic trioxide and paclitaxel on human malignant lymphocytes. Chem Biol Interact. 2010;183(1):222–30.CrossRefPubMed
15.
Ramirez P, Eastmond DA, Laclette JP, Ostrosky-Wegman P. Disruption of microtubule assembly and spindle formation as a mechanism for the induction of aneuploid cells by sodium arsenite and vanadium pentoxide. Mutat Res. 1997;386(3):291–8.CrossRefPubMed
16.
Di Cristofano A, Pandolfi PP. The multiple roles of PTEN in tumor suppression. Cell. 2000;100(4):387–90.CrossRefPubMed
17.
18.
19.
20.
Carracedo A, Pandolfi PP. The PTEN-PI3K pathway: of feedbacks and cross-talks. Oncogene. 2008;27(41):5527–41.CrossRefPubMed
21.
Berger AH, Pandolfi PP. Haplo-insufficiency: a driving force in cancer. J Pathol. 2011;223(2):137–46.CrossRefPubMed
22.
23.
24.
Shen WH, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell. 2007;128(1):157–70.CrossRefPubMed
25.
26.
Izawa D, Pines J. The mitotic checkpoint complex binds a second CDC20 to inhibit active APC/C. Nature. 2015;517(7536):631–4.CrossRefPubMed
27.
Choi BH, Pagano M, Huang C, Dai W. Cdh1, a substrate-recruiting component of anaphase-promoting complex/cyclosome (APC/C) ubiquitin E3 ligase, specifically interacts with phosphatase and tensin homolog (PTEN) and promotes its removal from chromatin. J Biol Chem. 2014;289(25):17951–9.CrossRefPubMedPubMedCentral
28.
Choi BH, Pagano M, Dai W. Plk1 protein phosphorylates phosphatase and tensin homolog (PTEN) and regulates its mitotic activity during the cell cycle. J Biol Chem. 2014;289(20):14066–74.CrossRefPubMedPubMedCentral
29.
Choi BH, Chen Y, Dai W. Chromatin PTEN is involved in DNA damage response partly through regulating Rad52 sumoylation. Cell Cycle. 2013;12(21):3442–7.CrossRefPubMedPubMedCentral
30.
Uzunova K, et al. APC15 mediates CDC20 autoubiquitylation by APC/C(MCC) and disassembly of the mitotic checkpoint complex. Nat Struct Mol Biol. 2012;19(11):1116–23.CrossRefPubMedPubMedCentral
31.
Bostock CJ, Prescott DM, Kirkpatrick JB. An evaluation of the double thymidine block for synchronizing mammalian cells at the G1-S border. Exp Cell Res. 1971;68(1):163–8.CrossRefPubMed
32.
Shedden K, Cooper S. Analysis of cell-cycle-specific gene expression in human cells as determined by microarrays and double-thymidine block synchronization. Proc Natl Acad Sci USA. 2002;99(7):4379–84.CrossRefPubMedPubMedCentral
33.
Li HY, Cao K, Zheng Y. Ran in the spindle checkpoint: a new function for a versatile GTPase. Trends Cell Biol. 2003;13(11):553–7.CrossRefPubMed
34.
Vitale I, Galluzzi L, Castedo M, Kroemer G. Mitotic catastrophe: a mechanism for avoiding genomic instability. Nat Rev Mol Cell Biol. 2011;12(6):385–92.CrossRefPubMed
35.
Mahata J, et al. Chromosomal aberrations in arsenic-exposed human populations: a review with special reference to a comprehensive study in West Bengal, India. Cytogenet Genome Res. 2004;104(1–4):359–64.CrossRefPubMed
36.
Dulout FN, et al. Chromosomal aberrations in peripheral blood lymphocytes from native Andean women and children from northwestern Argentina exposed to arsenic in drinking water. Mutat Res. 1996;370(3–4):151–8.CrossRefPubMed
37.
Basu A, et al. Enhanced frequency of micronuclei in individuals exposed to arsenic through drinking water in West Bengal, India. Mutat Res. 2002;516(1–2):29–40.CrossRefPubMed
38.
Yih LH, Lee TC. Induction of C-anaphase and diplochromosome through dysregulation of spindle assembly checkpoint by sodium arsenite in human fibroblasts. Cancer Res. 2003;63(20):6680–8.PubMed
39.
Patlolla AK, Tchounwou PB. Cytogenetic evaluation of arsenic trioxide toxicity in Sprague–Dawley rats. Mutat Res. 2005;587(1–2):126–33.CrossRefPubMed
40.
Chien CW, Chiang MC, Ho IC, Lee TC. Association of chromosomal alterations with arsenite-induced tumorigenicity of human HaCaT keratinocytes in nude mice. Environ Health Perspect. 2004;112(17):1704–10.CrossRefPubMedPubMedCentral
41.
Murayama-Hosokawa S, et al. Genome-wide single-nucleotide polymorphism arrays in endometrial carcinomas associate extensive chromosomal instability with poor prognosis and unveil frequent chromosomal imbalances involved in the PI3-kinase pathway. Oncogene. 2010;29(13):1897–908.CrossRefPubMed
42.
Hirai Y, et al. Somatic mutations of the PTEN/NMAC1 gene associated with frequent chromosomal loss detected using comparative genomic hybridization in endometrial cancer. Gynecol Oncol. 2001;83(1):81–8.CrossRefPubMed
43.
Leonard MK, Hill NT, Bubulya PA, Kadakia MP. The PTEN-Akt pathway impacts the integrity and composition of mitotic centrosomes. Cell Cycle. 2013;12(9):1406–15.CrossRefPubMedPubMedCentral
44.
Puc J, et al. Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer Cell. 2005;7(2):193–204.CrossRefPubMed
45.
Puc J, Parsons R. PTEN loss inhibits CHK1 to cause double stranded-DNA breaks in cells. Cell Cycle. 2005;4(7):927–9.CrossRefPubMed
46.
Huang J, et al. SUMO1 modification of PTEN regulates tumorigenesis by controlling its association with the plasma membrane. Nat Commun. 2010;3:911.CrossRef
47.
Metadata
Title
PTEN is a negative regulator of mitotic checkpoint complex during the cell cycle
Authors
Byeong H. Choi
Steve Xie
Wei Dai
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Experimental Hematology & Oncology / Issue 1/2017
Electronic ISSN: 2162-3619
DOI
https://doi.org/10.1186/s40164-017-0079-0

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