Top

Journal of Cancer Research and Clinical Oncology

Published in:

20-04-2022 | Review – Cancer Research

An approach to p32/gC1qR/HABP1: a multifunctional protein with an essential role in cancer

Authors: Carlos Alejandro Egusquiza-Alvarez, Martha Robles-Flores

Published in: Journal of Cancer Research and Clinical Oncology | Issue 8/2022

Abstract

P32/gC1qR/HABP1 is a doughnut-shaped acidic protein, highly conserved in eukaryote evolution and ubiquitous in the organism. Although its canonical subcellular localization is the mitochondria, p32 can also be found in the cytosol, nucleus, cytoplasmic membrane, and it can be secreted. Therefore, it is considered a multicompartmental protein. P32 can interact with many physiologically divergent ligands in each subcellular location and modulate their functions. The main ligands are C1q, hyaluronic acid, calreticulin, CD44, integrins, PKC, splicing factor ASF/SF2, and several microbial proteins. Among the functions in which p32 participates are mitochondrial metabolism and dynamics, apoptosis, splicing, immune response, inflammation, and modulates several cell signaling pathways. Notably, p32 is overexpressed in a significant number of epithelial tumors, where its expression level negatively correlates with patient survival. Several studies of gain and/or loss of function in cancer cells have demonstrated that p32 is a promoter of malignant hallmarks such as proliferation, cell survival, chemoresistance, angiogenesis, immunoregulation, migration, invasion, and metastasis. All of this strongly suggests that p32 is a potential diagnostic molecule and therapeutic target in cancer. Indeed, preclinical advances have been made in developing therapeutic strategies using p32 as a target. They include tumor homing peptides, monoclonal antibodies, an intracellular inhibitor, a p32 peptide vaccine, and p32 CAR T cells. These advances are promising and will allow soon to include p32 as part of targeted cancer therapies.

Bialucha CU et al (2007) p32 is a novel mammalian Lgl binding protein that enhances the activity of protein kinase Cζ and regulates cell polarity. J Cell Biol 178(4):575–581PubMedPubMedCentralCrossRef

Biswas AK et al (2007) Plasmodium falciparum uses gC1qR/HABP1/p32 as a receptor to bind to vascular endothelium and for platelet-mediated clumping. PLoS Pathog 3(9):1271–1280PubMedCrossRef

Braun L, Ghebrehiwet B, Cossart P (2000) GC1q-R/p32, a C1q-binding protein, is a receptor for the InlB invasion protein of listeria monocytogenes. EMBO J 19(7):1458–1466PubMedPubMedCentralCrossRef

Bruni R, Roizman B (1996) Open reading frame P - A herpes simplex virus gene repressed during productive infection encodes a protein that binds a splicing factor and reduces synthesis of viral proteins made from spliced mRNA. Proc Natl Acad Sci USA 93(19):10423–10427PubMedPubMedCentralCrossRef

Cancer, Burden O F. 2020. “WHO Cancer Report 2020 Global Profile.” www.paho.org.

“Cancer Facts & Figures 2020.” 2020. American Cancer Society.

Chattopadhyay C, Hawke D, Kobayashi R, Maity SN (2004) Human p32, interacts with B subunit of the CCAAT-binding factor, CBF/NF-Y, and inhibits CBF-mediated transcription activation in vitro. Nucleic Acids Res 32(12):3632–3641PubMedPubMedCentralCrossRef

Chen YB et al (2009) increased expression of hyaluronic acid binding protein 1 Is correlated with poor prognosis in patients with breast cancer. J Surg Oncol 100(5):382–386PubMedCrossRef

Choi Y et al (2008) A hantavirus causing hemorrhagic fever with renal syndrome requires gC1qR/p32 for efficient cell binding and infection. Virology 381(2):178–183. https://doi.org/10.1016/j.virol.2008.08.035CrossRefPubMed

Chowdhury AR, Ghosh I, Datta K (2008) Excessive reactive oxygen species induces apoptosis in fibroblasts: role of mitochondrially accumulated hyaluronic acid binding protein 1 (HABP1/p32/gC1qR). Exp Cell Res 314(3):651–667PubMedCrossRef

Chung HJ et al (2017) RAP80 binds p32 to preserve the functional integrity of mitochondria. Biochem Biophys Res Commun 492(3):441–446. https://doi.org/10.1016/j.bbrc.2017.08.077CrossRefPubMed

D’Souza M, Datta K (1985) Evidence for naturally occurring hyaluronic acid binding protein in rat liver. Biochem Int 10(1):43–51PubMed

D’Souza M, Datta K (1986) A novel glycoprotein that binds to hyaluronic acid. Biochem Int 13:79–88PubMed

Dang CV (2010) p32 (C1QBP) and cancer cell metabolism: is the warburg effect a lot of hot air? Mol Cell Biol 30(6):1300–1302PubMedPubMedCentralCrossRef

Deb TB, Datta K (1996) Molecular cloning of human fibroblast hyaluronic acid-binding protein confirms its identity with P-32, a protein co-purified with splicing factor SF2. J Biol Chem 271(4):2206–2212PubMedCrossRef

Dedio J, Jahnen-Dechent W, Bachmann M, Müller-Esterl W (1998) The multiligand-binding protein gC1qR, putative C1q receptor, is a mitochondrial protein. J Immunol 160:3534–3542PubMed

Dehghan-Manshadi Mahdi et al (2021) Protective immune response against P32 oncogenic peptide-pulsed PBMCs in mouse models of breast cancer. Int Immunopharmacol 93:107414. https://doi.org/10.1016/j.intimp.2021.107414CrossRefPubMed

Dembitzer FR et al (2012) gC1qR expression in normal and pathologic human tissues: differential expression in tissues of epithelial and mesenchymal origin. J Histochem Cytochem 60(6):467–474PubMedPubMedCentralCrossRef

Egusquiza-Alvarez CA et al (2021) Overexpression of Multifunctional protein p32 promotes a malignant phenotype in colorectal cancer cells. Front Oncol 11:1–15CrossRef

Even Y et al (2006) CDC2L5, a Cdk-like kinase with RS domain, interacts with the ASF/SF2-associated protein p32 and affects splicing in vivo. J Cell Biochem 99(3):890–904PubMedCrossRef

Fausther-Bovendo PH et al (2010) Hiv gp41 engages gc1qr on cd4+ T cells to induce the expression of an Nk ligand through the pip3/h2o2. PLoS Pathog 6(7):1–14CrossRef

Feng X, Tonnesen MG, Peerschke EIB, Ghebrehiwet B (2002) Cooperation of C1q receptors and integrins in C1q-mediated endothelial cell adhesion and spreading. J Immunol 168(5):2441–2448PubMedCrossRef

Fogal V, Zhang L, Krajewski S, Ruoslahti E (2008) Mitochondrial / cell-surface protein p32 / gC1qR as a molecular target in tumor cells and tumor stroma. Can Res 68(17):7210–7219CrossRef

Fogal V et al (2010) Mitochondrial p32 protein is a critical regulator of tumor metabolism via maintenance of oxidative phosphorylation. Mol Cell Biol 30(6):1303–1318PubMedPubMedCentralCrossRef

Fogal V et al (2015) Mitochondrial p32 is upregulated in Myc expressing brain cancers and mediates glutamine addiction. Oncotarget 6(2):1157–1170PubMedCrossRef

Ghate NB et al (2019) p32 Is a negative regulator of p53 tetramerization and transactivation. Mol Oncol 13:1976–1992PubMedPubMedCentralCrossRef

Ghebrehiwet B et al (1994) Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular ‘heads’ of C1q. J Exp Med 179(6):1809–1821PubMedCrossRef

Ghebrehiwet B, Lu PD, Zhang W, Keilbaugh SA, Leigh LE, Eggleton P, Reid KB, Peerschke EI (1996) Identification of functional domains on gClQ-R, a cell surface protein that binds to the globular ‘ heads ’ of C1Q, using monoclonal antibodies and synthetic peptides. Hybridoma 15(5):333–42PubMedCrossRef

Ghebrehiwet B et al (2001) gC1q-R / p33, a member of a new class of multifunctional and multicompartmental cellular proteins, is involved in inflammation and infection. Immunol Rev 180(180):65–77PubMedCrossRef

Ghebrehiwet B, Jesty J, Peerschkey EIB (2002) gC1q-R / p33: structure-function predictions from the crystal structure. Inmunobiology 205:421–432CrossRef

Ghebrehiwet B, Jesty J, Xu S, Vinayagasundaram R, Vinayagasundaram U, Peerschke EI, Ji Y, Valentino A, Hosszu KK, Mathew S, Joseph K, Kaplan AP (2011) Structure – function studies using deletion mutants identify domains of gC1qR / p33 as potential therapeutic targets for vascular permeability and inflammation. Front Inmunol 2:1–9

Ghebrehiwet B et al (2019) The C1q receptors: focus on gC1qR/p33 (C1qBP, p32, HABP-1). Semin Inmunol 45:1–14

Ghebrehiwet B et al (2007) The exosporium of B. cereus contains a binding site for gC1qR/p33: implication in spore attachment and/or entry. Exp Med Biol 23(1):1–7

Ghebrehiwet B et al (1997) Evidence that the two C1q binding membrane proteins, gC1q-R and cC1q-R, associate to form a complex. J Immunol 159(3):1429–36PubMed

Ghosh I, Chowdhury AR, Rajeswari MR, Datta K (2004) Differential expression of hyaluronic acid binding protein 1 (HABP1)/P32/C1QBP during progression of epidermal carcinoma. Mol Cell Biochem 267(1–2):133–139PubMedCrossRef

Gotoh K et al (2018) Mitochondrial p32/C1qbp is a critical regulator of dendritic cell metabolism and maturation. Cell Rep 25(7):1800-1815.e4. https://doi.org/10.1016/j.celrep.2018.10.057CrossRefPubMed

Guo N et al (1997) Assignment of C1QBP encoding the C1 Q globular domain binding protein (gCIq-R) to human chromosome 17 Band p13. 3 by in situ hybridization. Cytogenet Cell Genet 77:283–284PubMedCrossRef

Gupta S, Batchu RB, Datta K (1991) Purification, partial characterization of rat kidney hyaluronic acid binding protein and its localization on the cell surface. Eur J Cell Biol 56(58):67

Herwald H et al (1996) Isolation and characterization of the kininogen-binding protein p33 from endothelial cells: identity with the gClq receptor. J Biol Chem 271(22):13040–13047PubMedCrossRef

Heyd F, Carmo-Fonseca M, Möröy T (2008) Differential isoform expression and interaction with the p32 regulatory protein controls the subcellular localization of the splicing factor U2AF26. J Biol Chem 283(28):19636–19645PubMedCrossRef

Honoré B et al (1993) Cloning and expression of a cDNA covering the complete coding region of the P32 subunit of human pre-M RNA splicing factor SF2. Gene 134(2):283–287PubMedCrossRef

Hosszu KK et al (2012) DC-SIGN, C1q, and gC1qR Form a trimolecular receptor complex on the surface of monocyte-derived immature dendritic cells. Blood 120(6):1228–1236. https://doi.org/10.1182/blood-2011-07-369728CrossRefPubMedPubMedCentral

Hu MJ et al (2013) P32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival. Biochem J 453(3):381–391PubMedCrossRef

Huang LJ et al (2008) Human p32 is a novel FOXC1-interacting protein that regulates FOXC1 transcriptional activity in ocular cells. Invest Ophthalmol Vis Sci 49(12):5243–5249PubMedCrossRef

Hunt H et al (2017) Targeting of p32 in peritoneal carcinomatosis with intraperitoneal linTT1 peptide-guided pro-apoptotic nanoparticles. J Control Release 260:142–153. https://doi.org/10.1016/j.jconrel.2017.06.005CrossRefPubMedPubMedCentral

Jayarajan J et al (2020) Curcumin induces chemosensitization to doxorubicin in Duke’s type B coloadenocarcinoma cell line. Mol Biol Rep 47(10):7883–7892. https://doi.org/10.1007/s11033-020-05866-wCrossRefPubMed

Jha BK, Salunke DM, Datta K (2002) Disulfide bond formation through Cys186 facilitates functionally relevant dimerization of trimeric hyaluronan-binding protein 1 (HABP1)/p32/gC1qR. Eur J Biochem 269(1):298–306PubMedCrossRef

Jha BK, Salunke DM, Datta K (2003) Structural flexibility of multifunctional HABP1 may be important for regulating its binding to different ligands. J Biol Chem 278(30):27464–27472PubMedCrossRef

Jiang J, Zhang Y, Krainer AR, Xu RM (1999) Crystal structure of human p32, a doughnut-shaped acidic mitochondrial matrix protein. Proc Natl Acad Sci USA 96(7):3572–77PubMedPubMedCentralCrossRef

Jiao H et al (2015) Chaperone-like protein p32 regulates ULK1 stability and autophagy. Cell Death Differ 22(11):1812–1823PubMedPubMedCentralCrossRef

Kamal A, Datta K (2006) Upregulation of hyaluronan binding protein 1 (HABP1/p32/gC1qR) is associated with cisplatin induced apoptosis. Apoptosis 11(5):861–874PubMedCrossRef

Kandov E et al (2018) C1q and C1q receptors (gC1qR and cC1qR) as potential novel targets for therapy against breast cancer. Curr Trends Immunol 19:59–76

Kanki T et al (2004) Architectural role of mitochondrial transcription factor A in maintenance of human mitochondrial DNA. Mol Cell Biol 24(22):9823–9834PubMedPubMedCentralCrossRef

Kaul R et al (2012) Overexpression of hyaluronan-binding protein 1 (HABP1/p32/gC1qR) in HepG2 cells leads to increased hyaluronan synthesis and cell proliferation by up-regulation of cyclin D1 in AKT-dependent pathway. J Biol Chem 287(23):19750–19764PubMedPubMedCentralCrossRef

Kim KB et al (2011) Cell-surface receptor for complement component C1q (gC1qR) is a key regulator for lamellipodia formation and cancer metastasis. J Biol Chem 286(26):23093–23101PubMedPubMedCentralCrossRef

Kim BC et al (2016) Antibody neutralization of cell-surface gC1qR/HABP1/SF2-p32 prevents lamellipodia formation and tumorigenesis. Oncotarget 7(31):49972–49985PubMedPubMedCentralCrossRef

Kittlesen DJ et al (2000) Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation. J Clin Investig 106(10):1239–1249PubMedPubMedCentralCrossRef

Krainer AR, Mayeda A, Kozak D, Binns G (1991) Functional Expression of cloned human splicing factor SF2: homology to RNA-binding proteins, Ul 70K, and drosophila splicing regulators. Cell 66:383–394PubMedCrossRef

Li Y, Wan OW, Xie W, Chung KKK (2011) P32 regulates mitochondrial morphology and dynamics through parkin. Neuroscience 199:346–358PubMedCrossRef

Li K et al (2015) ZNF32 protects against oxidative stress-induced apoptosis by modulating C1QBP transcription. Oncotarget 6(35):38107–38126PubMedPubMedCentralCrossRef

Liebert MA et al (2002) Evidence for the presence of HABP1 pseudogene in multiple locations of mammalian genome. DNA Cell Biol 21(10):727–735CrossRef

Lim BL et al (1996) The binding protein for globular heads of complement C1q, gC1qR: functional expression and characterization as a novel vitronectin binding factor. J Biol Chem 271(43):26739–26744PubMedCrossRef

Lim B-L et al (1998) Characterization of the murine gene of gC1qBP, a novel cell protein that binds the globular heads of C1q, vitronectin, high molecular weight kininogen and factor XII 1. Gene 209:229–237PubMedCrossRef

Liu Y et al (2017) P32 heterozygosity protects against age-and diet-induced obesity by increasing energy expenditure. Sci Rep 7(1):1–10. https://doi.org/10.1038/s41598-017-06209-9CrossRef

Lu PD, Galanakis DK, Ghebrehiwet B, Peerschke EIB (1999) The receptor for the globular ‘heads’ of C1q, gC1q-R, binds to fibrinogen/fibrin and impairs its polymerization. Clin Immunol 90(3):360–367PubMedCrossRef

Lynch NJ et al (1997) Characterisation of the rat and mouse homologues of gClqBP, a 33 kDa glycoprotein that binds to the globular heads of Clq. FEBS Lett 418(1–2):111–114. https://doi.org/10.1016/S0014-5793(97)01348-3CrossRefPubMed

Ma J et al (2019) The expression pattern of p32 in sheep muscle and its role in differentiation, cell proliferation, and apoptosis of myoblasts. Int J Mol Sci 20(5161):1–18

Majumdar M, Datta K (1998) Assignment of cDNA encoding hyaluronic acid-binding protein 1 to human chromosome 17p12 – p13. Genomics 51:476–477PubMedCrossRef

Majumdar M, Meenakshi J, Datta K, Goswami SK (2002) Hyaluronan binding protein 1 (HABP1)/c1qbp/p32 Is an endogenous substrate for MAP kinase and is translocated to the nucleus upon mitogenic stimulation. Biochem Biophys Res Commun 291(4):829–837PubMedCrossRef

Mallick J, Datta K (2005) HABP1/p32/gC1qR induces aberrant growth and morphology in schizosaccharomyces pombe through its N-terminal α helix. Exp Cell Res 309(2):250–263PubMedCrossRef

Rao CM, Deb TB, Datta K (1996) Hyaluronic acid induced hyaluronic binding protein phosphorylation and inositol triphosphate formation in lymphocytes. Biochem Mol Biol Int 40(2):327–337PubMed

Matthews DA, Russell WC (1998) Adenovirus core protein V interacts with p32 – a protein which is associated with both the mitochondria and the nucleus. J Gen Virol 79:1677–1685PubMedCrossRef

McGee AM et al (2011) The mitochondrial protein C1qbp promotes cell proliferation, migration and resistance to cell death. Cell Cycle 10(23):4119–4127PubMedPubMedCentralCrossRef

McGee A, Baineswe CP (2011) Complement 1q-binding protein inhibits the mitochondrial permeability transition pore and protects against oxidative stress-induced death. Biochem J 433(1):119–25PubMedCrossRef

Meenakshi J, Anupama, Goswami SK, Datta K (2003) Constitutive expression of hyaluronan binding protein 1 (HABP1/p32/gC1qR) in normal fibroblast cells perturbs its growth characteristics and induces apoptosis. Biochem Biophys Res Commun 300(3):686–93PubMedCrossRef

Mohan KV, Krishna BG, Atreya CD (2002) The N-terminal conserved domain of rubella virus capsid interacts with the C-terminal region of cellular p32 and overexpression of p32 enhances the viral infectivity. Virus Res 85(2):151–161PubMedCrossRef

Muta T et al (1997) p32 protein, a splicing factor 2-associated protein, is localized in mitochondrial matrix and is functionally important in maintaining oxidative phosphorylation *. J Biol Chem 272(39):24363–24370PubMedCrossRef

Nguyen T, Ghebrehiwet B, Peerschke EIB (2000) Staphylococcus aureus protein A recognizes platelet gC1qR/p33: a novel mechanism for staphylococcal interactions with platelets. Infect Immun 68(4):2061–2068PubMedPubMedCentralCrossRef

Niu M et al (2015) Elevated expression of HABP1 is correlated with metastasis and poor survival in breast cancer patients. Am J Cancer Res 5(3):1190–98PubMedPubMedCentral

Noh S et al (2020) p32/C1QBP regulates OMA1-dependent proteolytic processing of OPA1 to maintain mitochondrial connectivity related to mitochondrial dysfunction and apoptosis. Sci Rep 10(1):1–16. https://doi.org/10.1038/s41598-020-67457-wCrossRef

Peerschke EIB, Ghebrehiwet B (2014) cC1qR / CR and gC1qR / p33: observations in cancer. Mol Immunol 61(2):100–109. https://doi.org/10.1016/j.molimm.2014.06.011CrossRefPubMed

Peerschke EIB, Brandwijk RJM, Dembitzer FR, Kinoshita Y, Ghebrehiwet B (2015) Soluble gC1qR in blood and body fluids: examination in a pancreatic cancer patient cohort. Int J Cancer Res Mol Mech 1(3):1–5

Peerschke E et al (2020a) gC1qR/HABP1/p32 Is a potential new therapeutic target against mesothelioma. Front Oncol 10:1–10CrossRef

Peerschke E et al (2020b) Anti gC1qR/p32/HABP1 antibody therapy decreases tumor growth in an orthotopic murine xenotransplant model of triple negative breast cancer. Antibodies 9(4):51PubMedCentralCrossRef

Petersen-Mahrt SK et al (1999) The splicing factor-associated protein, p32, regulates RNA splicing by inhibiting ASF/SF2 RNA binding and phosphorylation. EMBO J 18(4):1014–1024PubMedPubMedCentralCrossRef

Prakash M et al (2011) Hyaluronan-binding protein 1 (HABP1/p32/gC1qR) induces melanoma cell migration and tumor growth by NF-Kappa B dependent MMP-2 activation through integrin α vβ 3 interaction. Cell Signal 23(10):1563–1577. https://doi.org/10.1016/j.cellsig.2011.04.009CrossRefPubMed

Raschdorf A et al (2021) Heterozygous P32/C1QBP/HABP1 polymorphism rs56014026 reduces mitochondrial oxidative phosphorylation and is expressed in low-grade colorectal carcinomas. Front Oncol 10:1–17CrossRef

Reef S, Shifman O, Oren M, Kimchi A (2007) The autophagic inducer smARF interacts with and is stabilized by the mitochondrial p32 protein. Oncogene 26(46):6677–6683PubMedCrossRef

Robles-Flores M et al (2002) p32 (gC1qBP) Is a general protein kinase C (PKC)-binding protein. Interaction and cellular localization of p32-PKC complexes in rat hepatocytes. J Biol Chem 277(7):5247–5255PubMedCrossRef

Rousso-Noori L et al (2021) P32-specific CAR T cells with dual antitumor and antiangiogenic therapeutic potential in gliomas. Nat Commun 12(1):1–13. https://doi.org/10.1038/s41467-021-23817-2CrossRef

Rozanov DV et al (2002) The Hemopexin-like C-terminal domain of membrane type 1 matrix metalloproteinase regulates proteolysis of a multifunctional protein, gC1qR. J Biol Chem 277(11):9318–9325PubMedCrossRef

Rubinstein DB et al (2004) Receptor for the globular heads of C1q (gC1q-R, p33, hyaluronan-binding protein) Is preferentially expressed by adenocarcinoma cells. Int J Cancer 110(5):741–750PubMedCrossRef

Saha S et al (2019) Systematic multiomics analysis of alterations in C1QBP mRNA expression and relevance for clinical outcomes in cancers. J Clin Med 8(513):1–16

Saha P, Datta K (2018) Multifuctional, multicompartmental hyaluronan-binding protein 1 (HABP1/p32/gC1qR): implication in cancer progression and metastasis. Oncotarget 9(12):10784–807PubMedPubMedCentralCrossRef

Saito T et al (2017) Cardiomyocyte-specific loss of mitochondrial p32/C1qbp causes cardiomyopathy and activates stress responses. Cardiovasc Res 113(10):1173–1185PubMedCrossRef

Sánchez-Martín D et al (2011) The multicompartmental p32/gClqR as a new target for antibody-based tumor targeting strategies. J Biol Chem 286(7):5197–5203PubMedCrossRef

Satarupa D, Deb TB, Kumar R, Datta K (1997) Multifunctional activities of human fibroblast 34-kDa hyaluronic acid-binding protein. Gene 190(1):223–225CrossRef

Schaerer MT et al (2001) Interaction between GABAA receptor β subunits and the multifunctional protein gC1q-R. J Biol Chem 276(28):26597–26604PubMedCrossRef

Seytter T, Lottspeich F, Neupert W, Schwarz E (1998) Mam33p, an oligomeric, acidic protein in the mitochondrial matrix of saccharomyces cerevisiae is related to the human complement receptor gC1q-R. Yeast 14:303–310PubMedCrossRef

Shi H, Fang W, Liu M, Deliang Fu (2017) Complement component 1, Q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF-1/IGF-1R signaling. Int J Cancer 141(7):1389–1401PubMedCrossRef

Simos G, Georgatos SD (1994) The lamin B receptor-associated protein p34 shares sequence homology and antigenic determinants with the splicing factor 2-associated protein p32. FEBS Lett 346(2–3):225–228PubMed

Sinha S et al (2021) p32 promotes melanoma progression and metastasis by targeting EMT markers, Akt/PKB pathway, and tumor microenvironment. Cell Death Dis 12(11):1–12CrossRef

Storz P et al (2000) Protein kinase C μ Is regulated by the multifunctional chaperon protein p32. J Biol Chem 275(32):24601–24607PubMedCrossRef

Sunayama J et al (2004) Physical and functional interaction between BH3-only protein Hrk and mitochondrial pore-forming protein p32. Cell Death Differ 11(7):771–781PubMedCrossRef

Sünderhauf A et al (2020) GC1qR cleavage by caspase-1 drives aerobic glycolysis in tumor cells. Front Oncol 10:1–16CrossRef

Sünderhauf A et al (2021) Loss of mucosal p32/gC1qR/HABP1 triggers energy deficiency and impairs goblet cell differentiation in ulcerative colitis. Cell Mol Gastroenterol Hepatol 12(1):229–250PubMedPubMedCentralCrossRef

Tange TØ, Jensen TH, Kjems J (1996) In vitro interaction between human immunodeficiency virus type 1 rev protein and splicing factor ASF/SF2-associated protein, p32. J Biol Chem 271(17):10066–10072PubMedCrossRef

Timur SS et al (2017) Molecular dynamics, thermodynamic, and mutational binding studies for tumor-specific LyP-1 in complex with p32. J Biomol Struct Dyn 36(5):1134–1144. https://doi.org/10.1080/07391102.2017.1313779CrossRefPubMed

Waggoner SN, Cruise MW, Kassel R, Hahn YS (2005) gC1q receptor ligation selectively down-regulates human IL-12 production through activation of the phosphoinositide 3-kinase pathway. J Immunol 175(7):4706–4714PubMedCrossRef

Wang Y, Finan JE, Middeldorp JM, Diane Hayward S (1997) P32/TAP, a cellular protein that interacts with EBNA-1 of Epstein-Barr Virus. Virology 236(1):18–29PubMedCrossRef

Wang JT et al (2014) Impaired p32 regulation caused by the lymphoma-prone RECQ4 mutation drives mitochondrial dysfunction. Cell Rep 7(3):848–858. https://doi.org/10.1016/j.celrep.2014.03.037CrossRefPubMedPubMedCentral

Wang Ji et al (2015) Elevated expression of HABP1 is a novel prognostic indicator in triple-negative breast cancers. Tumor Biol 36(6):4793–4799CrossRef

Watthanasurorot A, Jiravanichpaisal P, Söderhäll K, Söderhäll I (2013) A calreticulin/gC1qR complex prevents cells from dying: a conserved mechanism from arthropods to humans. J Mol Cell Biol 5(2):120–131PubMedCrossRef

Wu H et al (2021) Hypoxia-mediated complement 1q binding protein regulates metastasis and chemoresistance in triple-negative breast cancer and modulates the PKC-NF-κB-VCAM-1 signaling pathway. Front Cell Dev Biol 9:1–21

Wu H et al (2013) Human RNase H1 is associated with protein P32 and is involved in mitochondrial pre-rRNA processing. PLoS One 8(8):e71006PubMedPubMedCentralCrossRef

Xiao K et al (2014) P32, a novel binding partner of Mcl-1, positively regulates mitochondrial Ca2+ uptake and apoptosis. Biochem Biophys Res Commun 451(2):322–328. https://doi.org/10.1016/j.bbrc.2014.07.122CrossRefPubMed

Xu Z, Hirasawa A, Shinoura H, Tsujimoto G (1999) Interaction of the α(1B)-adrenergic receptor with gC1q-R, a multifunctional protein. J Biol Chem 274(30):21149–21154PubMedCrossRef

Xu J et al (2020a) Globular C1q receptor (gC1qR/p32/HABP1) suppresses the tumor-inhibiting role of C1q and promotes tumor proliferation in 1q21-amplified multiple myeloma. Front Immunol 11:1–17CrossRef

Xu W et al (2020b) LyP-1-modified oncolytic adenoviruses targeting transforming growth factor β inhibit tumor growth and metastases and augment immune checkpoint inhibitor therapy in breast cancer mouse models. Hum Gene Ther 31(15–16):863–880PubMedPubMedCentralCrossRef

Yadav G et al (2009) Evidence for inhibitory interaction of hyaluronan-binding protein 1 (HABP1/p32/gC1 qR) with streptococcus pneumoniae hyaluronidase. J Biol Chem 284(6):3897–3905PubMedCrossRef

Yagi M et al (2012) P32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA-binding ability. Nucleic Acids Res 40(19):9717–9737PubMedPubMedCentralCrossRef

Yenugonda V et al (2017) A novel small molecule inhibitor of p32 mitochondrial protein overexpressed in glioma. J Transl Med 15(1):1–12CrossRef

Yoshikawa H et al (2011) Splicing factor 2-associated protein p32 participates in ribosome biogenesis by regulating the binding of Nop52 and fibrillarin to preribosome particles. Mol Cell Proteomics 10(8):1–23CrossRef

Yu G, Wang J (2013) Significance of hyaluronan binding protein (HABP1/P32/gC1qR) expression in advanced serous ovarian cancer patients. Exp Mol Pathol 94(1):210–215PubMedCrossRef

Yu L, Loewenstein PM, Zhang Z, Green M (1995) In vitro interaction of the human immunodeficiency virus type 1 Tat transactivator and the general transcription factor TFIIB with the cellular protein TAP. J Virol 69(5):3017–3023PubMedPubMedCentralCrossRef

Zhang X et al (2013) Interactome analysis reveals that C1QBP (complement component 1, Q subcomponent binding protein) is associated with cancer cell chemotaxis and metastasis. Mol Cell Proteomics 12(11):3199–3209PubMedPubMedCentralCrossRef

Zhang M et al (2017) Hyaluronic acid binding protein 1 overexpression is an indicator for disease-free survival in cervical cancer. Int J Clin Oncol 22(2):347–352PubMedCrossRef

Zhao J, Liu T, Ge Yu, Wang J (2015) Overexpression of HABP1 correlated with clinicopathological characteristics and unfavorable prognosis in endometrial cancer. Tumor Biol 36(2):1299–1306CrossRef

Title: An approach to p32/gC1qR/HABP1: a multifunctional protein with an essential role in cancer
Authors: Carlos Alejandro Egusquiza-Alvarez
Martha Robles-Flores
Publication date: 20-04-2022
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 8/2022
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-022-04001-5

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 8/2022

Transformation of invasive lung adenocarcinoma with ALK rearrangement into pulmonary sarcomatoid carcinoma

Quality of life in lung cancer survivors treated with tyrosine-kinase inhibitors (TKI): results from the multi-centre cross-sectional German study LARIS

iRECIST-based versus non-standardized free text reporting of CT scans for monitoring metastatic renal cell carcinoma: a retrospective comparison

First and repeat rebiopsy for detecting EGFR T790M mutation in non-small-cell lung cancer: CS-Lung-003 prospective observational registry study

Evolution of predictive and prognostic biomarkers in the treatment of advanced gastric cancer

Correction: Investigation of the protective effect of gel incorporating Eugenia jambolana leaf extract on 5-fluorouracil-induced oral mucositis: an animal study

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials