Protein Phosphatase 2A Regulatory Subunit B56α Associates with c-Myc and Negatively Regulates c-Myc Accumulation

REFERENCES

• Agostinis, P., R. Derua, S. Sarno, J. Goris, and W. Merlevede. 1992. Specificity of the polycation-stimulated (type-2A) and ATP, Mg-dependent (type-1) protein phosphatases toward substrates phosphorylated by P34cdc2 kinase. Eur. J. Biochem. 205:241–248.
   PubMedGoogle Scholar
• Al-Murrani, S. W., J. R. Woodgett, and Z. Damuni. 1999. Expression of I2PP2A, an inhibitor of protein phosphatase 2A, induces c-Jun and AP-1 activity. Biochem. J. 341:293–298.
   PubMed Web of Science ®Google Scholar
• Altiok, S., M. Xu, and B. M. Spiegelman. 1997. PPARgamma induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes Dev. 11:1987–1998.
   PubMed Web of Science ®Google Scholar
• Andjelkovic, N., S. Zolnierowicz, C. Van Hoof, J. Goris, and B. A. Hemmings. 1996. The catalytic subunit of protein phosphatase 2A associates with the translation termination factor eRF1. EMBO J. 15:7156–7167.
   PubMedGoogle Scholar
• Chang, D. W., G. F. Claassen, S. R. Hann, and M. D. Cole. 2000. The c-Myc transactivation domain is a direct modulator of apoptotic versus proliferative signals. Mol. Cell. Biol. 20:4309–4319.
   PubMed Web of Science ®Google Scholar
• Chen, J., J. R. St.-Germain, and Q. Li. 2005. B56 regulatory subunit of protein phosphatase 2A mediates valproic acid-induced p300 degradation. Mol. Cell. Biol. 25:525–532.
   PubMed Web of Science ®Google Scholar
• Chen, W., R. Possemato, K. T. Campbell, C. A. Plattner, D. C. Pallas, and W. C. Hahn. 2004. Identification of specific PP2A complexes involved in human cell transformation. Cancer Cell 5:127–136.
   PubMed Web of Science ®Google Scholar
• Cole, M. D. 1986. The myc oncogene: its role in transformation and differentiation. Annu. Rev. Genet. 20:361–384.
   PubMed Web of Science ®Google Scholar
• Csortos, C., S. Zolnierowicz, E. Bako, S. D. Durbin, and A. A. DePaoli-Roach. 1996. High complexity in the expression of the B′ subunit of protein phosphatase 2A0. Evidence for the existence of at least seven novel isoforms. J. Biol. Chem. 271:2578–2588.
   PubMedGoogle Scholar
• Dang, C. V., L. M. Resar, E. Emison, S. Kim, Q. Li, J. E. Prescott, D. Wonsey, and K. Zeller. 1999. Function of the c-Myc oncogenic transcription factor. Exp. Cell Res. 253:63–77.
   PubMed Web of Science ®Google Scholar
• Davis, A. C., M. Wims, G. D. Spotts, S. R. Hann, and A. Bradley. 1993. A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice. Genes Dev. 7:671–682.
   PubMed Web of Science ®Google Scholar
• de Alboran, I. M., R. C. O'Hagan, F. Gartner, B. Malynn, L. Davidson, R. Rickert, K. Rajewsky, R. A. DePinho, and F. W. Alt. 2001. Analysis of C-MYC function in normal cells via conditional gene-targeted mutation. Immunity 14:45–55.
   PubMed Web of Science ®Google Scholar
• Dozier, C., M. Bonyadi, L. Baricault, L. Tonasso, and J. M. Darbon. 2004. Regulation of Chk2 phosphorylation by interaction with protein phosphatase 2A via its B′ regulatory subunit. Biol. Cell. 96:509–517.
   PubMedGoogle Scholar
• Evan, G. I., A. H. Wyllie, C. S. Gilbert, T. D. Littlewood, H. Land, M. Brooks, C. M. Waters, L. Z. Penn, and D. C. Hancock. 1992. Induction of apoptosis in fibroblasts by c-myc protein. Cell 69:119–128.
   PubMed Web of Science ®Google Scholar
• Felsher, D. W., and J. M. Bishop. 1999. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol. Cell 4:199–207.
   PubMed Web of Science ®Google Scholar
• Fernandez, J. J., M. L. Candenas, M. L. Souto, M. M. Trujillo, and M. Norte. 2002. Okadaic acid, useful tool for studying cellular processes. Curr. Med. Chem. 9:229–262.
   PubMed Web of Science ®Google Scholar
• Flinn, E. M., C. M. Busch, and A. P. Wright. 1998. Myc boxes, which are conserved in Myc family proteins, are signals for protein degradation via the proteasome. Mol. Cell. Biol. 18:5961–5969.
   PubMedGoogle Scholar
• Gotz, J., A. Probst, E. Ehler, B. Hemmings, and W. Kues. 1998. Delayed embryonic lethality in mice lacking protein phosphatase 2A catalytic subunit Calpha. Proc. Natl. Acad. Sci. USA 95:12370–12375.
   PubMedGoogle Scholar
• Gregory, M. A., and S. R. Hann. 2000. c-Myc proteolysis by the ubiquitin-proteasome pathway: stabilization of c-Myc in Burkitt's lymphoma cells. Mol. Cell. Biol. 20:2423–2435.
   PubMed Web of Science ®Google Scholar
• Hahn, W. C., S. K. Dessain, M. W. Brooks, J. E. King, B. Elenbaas, D. M. Sabatini, J. A. DeCaprio, and R. A. Weinberg. 2002. Enumeration of the simian virus 40 early region elements necessary for human cell transformation. Mol. Cell. Biol. 22:2111–2123.
   PubMed Web of Science ®Google Scholar
• Hemann, M. T., A. Bric, J. Teruya-Feldstein, A. Herbst, J. A. Nilsson, C. Cordon-Cardo, J. L. Cleveland, W. P. Tansey, and S. W. Lowe. 2005. Evasion of the p53 tumour surveillance network by tumour-derived MYC mutants. Nature 436:807–811.
   PubMed Web of Science ®Google Scholar
• Henriksson, M., A. Bakardjiev, G. Klein, and B. Luscher. 1993. Phosphorylation sites mapping in the N-terminal domain of c-myc modulate its transforming potential. Oncogene 8:3199–3209.
   PubMedGoogle Scholar
• Ito, A., T. R. Kataoka, M. Watanabe, K. Nishiyama, Y. Mazaki, H. Sabe, Y. Kitamura, and H. Nojima. 2000. A truncated isoform of the PP2A B56 subunit promotes cell motility through paxillin phosphorylation. EMBO J. 19:562–571.
   PubMed Web of Science ®Google Scholar
• Ito, A., Y. Koma, K. Watabe, T. Nagano, Y. Endo, H. Nojima, and Y. Kitamura. 2003. A truncated isoform of the protein phosphatase 2A B56gamma regulatory subunit may promote genetic instability and cause tumor progression. Am. J. Pathol. 162:81–91.
   PubMedGoogle Scholar
• Janssens, V., and J. Goris. 2001. Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem. J. 353:417–439.
   PubMed Web of Science ®Google Scholar
• Jones, T. R., and M. D. Cole. 1987. Rapid cytoplasmic turnover of c-myc mRNA: requirement of the 3′ untranslated sequences. Mol. Cell. Biol. 7:4513–4521.
   PubMed Web of Science ®Google Scholar
• Kanopka, A., O. Muhlemann, S. Petersen-Mahrt, C. Estmer, C. Ohrmalm, and G. Akusjarvi. 1998. Regulation of adenovirus alternative RNA splicing by dephosphorylation of SR proteins. Nature 393:185–187.
   PubMed Web of Science ®Google Scholar
• Keen, J. C., Q. Zhou, B. H. Park, C. Pettit, K. M. Mack, B. Blair, K. Brenner, and N. E. Davidson. 2005. Protein phosphatase 2A regulates estrogen receptor alpha (ER) expression through modulation of ER mRNA stability. J. Biol. Chem. 280:29519–29524.
   PubMed Web of Science ®Google Scholar
• Kelly, K., B. H. Cochran, C. D. Stiles, and P. Leder. 1983. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 35:603–610.
   PubMed Web of Science ®Google Scholar
• Kleinberger, T., and T. Shenk. 1993. Adenovirus E4orf4 protein binds to protein phosphatase 2A, and the complex down regulates E1A-enhanced junB transcription. J. Virol. 67:7556–7560.
   PubMedGoogle Scholar
• Kremmer, E., K. Ohst, J. Kiefer, N. Brewis, and G. Walter. 1997. Separation of PP2A core enzyme and holoenzyme with monoclonal antibodies against the regulatory A subunit: abundant expression of both forms in cells. Mol. Cell. Biol. 17:1692–1701.
   PubMedGoogle Scholar
• Lechward, K., S. Zolnierowicz, and B. A. Hemmings. 1999. Eukaryotic translation termination factor 1 associates with protein phosphatase 2A and targets it to ribosomes. Biochemistry (Moscow) 64:1373–1381.
   PubMed Web of Science ®Google Scholar
• Li, X., and D. M. Virshup. 2002. Two conserved domains in regulatory B subunits mediate binding to the A subunit of protein phosphatase 2A. Eur. J. Biochem. 269:546–552.
   PubMedGoogle Scholar
• Li, X., H. J. Yost, D. M. Virshup, and J. M. Seeling. 2001. Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus. EMBO J. 20:4122–4131.
   PubMedGoogle Scholar
• Lutterbach, B., and S. R. Hann. 1994. Hierarchical phosphorylation at N-terminal transformation-sensitive sites in c-Myc protein is regulated by mitogens and in mitosis. Mol. Cell. Biol. 14:5510–5522.
   PubMed Web of Science ®Google Scholar
• Martens, E., I. Stevens, V. Janssens, J. Vermeesch, J. Gotz, J. Goris, and C. Van Hoof. 2004. Genomic organisation, chromosomal localisation tissue distribution and developmental regulation of the PR61/B′ regulatory subunits of protein phosphatase 2A in mice. J. Mol. Biol. 336:971–986.
   PubMedGoogle Scholar
• Mayer-Jaekel, R. E., H. Ohkura, P. Ferrigno, N. Andjelkovic, K. Shiomi, T. Uemura, D. M. Glover, and B. A. Hemmings. 1994. Drosophila mutants in the 55 kDa regulatory subunit of protein phosphatase 2A show strongly reduced ability to dephosphorylate substrates of p34cdc2. J. Cell Sci. 107:2609–2616.
   PubMedGoogle Scholar
• McCright, B., A. R. Brothman, and D. M. Virshup. 1996. Assignment of human protein phosphatase 2A regulatory subunit genes b56alpha, b56beta, b56gamma, b56delta, and b56epsilon (PPP2R5A-PPP2R5E), highly expressed in muscle and brain, to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.2→p12. Genomics 36:168–170.
   PubMedGoogle Scholar
• McCright, B., A. M. Rivers, S. Audlin, and D. M. Virshup. 1996. The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm. J. Biol. Chem. 271:22081–22089.
   PubMed Web of Science ®Google Scholar
• McCright, B., and D. M. Virshup. 1995. Identification of a new family of protein phosphatase 2A regulatory subunits. J. Biol. Chem. 270:26123–26128.
   PubMedGoogle Scholar
• Mumby, M. 1995. Regulation by tumour antigens defines a role for PP2A in signal transduction. Semin. Cancer Biol. 6:229–237.
   PubMedGoogle Scholar
• Nowak, S. J., C. Y. Pai, and V. G. Corces. 2003. Protein phosphatase 2A activity affects histone H3 phosphorylation and transcription in Drosophila melanogaster. Mol. Cell. Biol. 23:6129–6138.
   PubMedGoogle Scholar
• Okamoto, K., C. Kamibayashi, M. Serrano, C. Prives, M. C. Mumby, and D. Beach. 1996. p53-dependent association between cyclin G and the B′ subunit of protein phosphatase 2A. Mol. Cell. Biol. 16:6593–6602.
   PubMed Web of Science ®Google Scholar
• Okamoto, K., H. Li, M. R. Jensen, T. Zhang, Y. Taya, S. S. Thorgeirsson, and C. Prives. 2002. Cyclin G recruits PP2A to dephosphorylate Mdm2. Mol. Cell 9:761–771.
   PubMed Web of Science ®Google Scholar
• Pallas, D. C., L. K. Shahrik, B. L. Martin, S. Jaspers, T. B. Miller, D. L. Brautigan, and T. M. Roberts. 1990. Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A. Cell 60:167–176.
   PubMed Web of Science ®Google Scholar
• Patturajan, M., S. Nomoto, M. Sommer, A. Fomenkov, K. Hibi, R. Zangen, N. Poliak, J. Califano, B. Trink, E. Ratovitski, and D. Sidransky. 2002. DeltaNp63 induces beta-catenin nuclear accumulation and signaling. Cancer Cell 1:369–379.
   PubMedGoogle Scholar
• Pelengaris, S., T. Littlewood, M. Khan, G. Elia, and G. Evan. 1999. Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion. Mol. Cell 3:565–577.
   PubMed Web of Science ®Google Scholar
• Pulverer, B. J., C. Fisher, K. Vousden, T. Littlewood, G. Evan, and J. R. Woodgett. 1994. Site-specific modulation of c-Myc cotransformation by residues phosphorylated in vivo. Oncogene 9:59–70.
   PubMed Web of Science ®Google Scholar
• Ruediger, R., M. Hentz, J. Fait, M. Mumby, and G. Walter. 1994. Molecular model of the A subunit of protein phosphatase 2A: interaction with other subunits and tumor antigens. J. Virol. 68:123–129.
   PubMedGoogle Scholar
• Ruediger, R., H. T. Pham, and G. Walter. 2001. Alterations in protein phosphatase 2A subunit interaction in human carcinomas of the lung and colon with mutations in the A beta subunit gene. Oncogene 20:1892–1899.
   PubMed Web of Science ®Google Scholar
• Ruediger, R., H. T. Pham, and G. Walter. 2001. Disruption of protein phosphatase 2A subunit interaction in human cancers with mutations in the A alpha subunit gene. Oncogene 20:10–15.
   PubMed Web of Science ®Google Scholar
• Ruediger, R., D. Roeckel, J. Fait, A. Bergqvist, G. Magnusson, and G. Walter. 1992. Identification of binding sites on the regulatory A subunit of protein phosphatase 2A for the catalytic C subunit and for tumor antigens of simian virus 40 and polyomavirus. Mol. Cell. Biol. 12:4872–4882.
   PubMedGoogle Scholar
• Rundell, K., and R. Parakati. 2001. The role of the SV40 ST antigen in cell growth promotion and transformation. Semin. Cancer Biol. 11:5–13.
   PubMed Web of Science ®Google Scholar
• Ruvolo, P. P., W. Clark, M. Mumby, F. Gao, and W. S. May. 2002. A functional role for the B56 alpha-subunit of protein phosphatase 2A in ceramide-mediated regulation of Bcl2 phosphorylation status and function. J. Biol. Chem. 277:22847–22852.
   PubMedGoogle Scholar
• Schonthal, A. H. 2001. Role of serine/threonine protein phosphatase 2A in cancer. Cancer Lett 170:1–13.
   PubMed Web of Science ®Google Scholar
• Sears, R., G. Leone, J. DeGregori, and J. R. Nevins. 1999. Ras enhances Myc protein stability. Mol. Cell 3:169–179.
   PubMed Web of Science ®Google Scholar
• Sears, R., F. Nuckolls, E. Haura, Y. Taya, K. Tamai, and J. R. Nevins. 2000. Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability. Genes Dev. 14:2501–2514.
   PubMed Web of Science ®Google Scholar
• Sears, R., K. Ohtani, and J. R. Nevins. 1997. Identification of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals. Mol. Cell. Biol. 17:5227–5235.
   PubMedGoogle Scholar
• Seeling, J. M., J. R. Miller, R. Gil, R. T. Moon, R. White, and D. M. Virshup. 1999. Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase 2A. Science 283:2089–2091.
   PubMed Web of Science ®Google Scholar
• Shtrichman, R., R. Sharf, H. Barr, T. Dobner, and T. Kleinberger. 1999. Induction of apoptosis by adenovirus E4orf4 protein is specific to transformed cells and requires an interaction with protein phosphatase 2A. Proc. Natl. Acad. Sci. USA 96:10080–10085.
   PubMed Web of Science ®Google Scholar
• Shtrichman, R., R. Sharf, and T. Kleinberger. 2000. Adenovirus E4orf4 protein interacts with both Balpha and B′ subunits of protein phosphatase 2A, but E4orf4-induced apoptosis is mediated only by the interaction with Balpha. Oncogene 19:3757–3765.
   PubMedGoogle Scholar
• Sontag, E., S. Fedorov, C. Kamibayashi, D. Robbins, M. Cobb, and M. Mumby. 1993. The interaction of SV40 small tumor antigen with protein phosphatase 2A stimulates the MAP kinase pathway and induces cell proliferation. Cell 75:887–897.
   PubMed Web of Science ®Google Scholar
• Strack, S., R. Ruediger, G. Walter, R. K. Dagda, C. A. Barwacz, and J. T. Cribbs. 2002. Protein phosphatase 2A holoenzyme assembly: identification of contacts between B-family regulatory and scaffolding A subunits. J. Biol. Chem. 277:20750–20755.
   PubMedGoogle Scholar
• Trumpp, A., Y. Refaeli, T. Oskarsson, S. Gasser, M. Murphy, G. R. Martin, and J. M. Bishop. 2001. c-Myc regulates mammalian body size by controlling cell number but not cell size. Nature 414:768–773.
   PubMed Web of Science ®Google Scholar
• Turowski, P., B. Favre, K. S. Campbell, N. J. Lamb, and B. A. Hemmings. 1997. Modulation of the enzymatic properties of protein phosphatase 2A catalytic subunit by the recombinant 65-kDa regulatory subunit PR65alpha. Eur. J. Biochem. 248:200–208.
   PubMedGoogle Scholar
• Turowski, P., T. Myles, B. A. Hemmings, A. Fernandez, and N. J. Lamb. 1999. Vimentin dephosphorylation by protein phosphatase 2A is modulated by the targeting subunit B55. Mol. Biol. Cell. 10:1997–2015.
   PubMed Web of Science ®Google Scholar
• Van Hoof, C., and J. Goris. 2004. PP2A fulfills its promises as tumor suppressor: which subunits are important? Cancer Cell 5:105–106.
   PubMed Web of Science ®Google Scholar
• Voorhoeve, P. M., E. M. Hijmans, and R. Bernards. 1999. Functional interaction between a novel protein phosphatase 2A regulatory subunit, PR59, and the retinoblastoma-related p107 protein. Oncogene 18:515–524.
   PubMed Web of Science ®Google Scholar
• Wadzinski, B. E., B. J. Eisfelder, L. F. Peruski, Jr., M. C. Mumby, and G. L. Johnson. 1992. NH2-terminal modification of the phosphatase 2A catalytic subunit allows functional expression in mammalian cells. J. Biol. Chem. 267:16883–16888.
   PubMedGoogle Scholar
• Wadzinski, B. E., W. H. Wheat, S. Jaspers, L. F. Peruski, Jr., R. L. Lickteig, G. L. Johnson, and D. J. Klemm. 1993. Nuclear protein phosphatase 2A dephosphorylates protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation. Mol. Cell. Biol. 13:2822–2834.
   PubMed Web of Science ®Google Scholar
• Wang, S. S., E. D. Esplin, J. L. Li, L. Huang, A. Gazdar, J. Minna, and G. A. Evans. 1998. Alterations of the PPP2R1B gene in human lung and colon cancer. Science 282:284–287.
   PubMed Web of Science ®Google Scholar
• Welcker, M., A. Orian, J. Jin, J. A. Grim, J. W. Harper, R. N. Eisenman, and B. E. Clurman. 2004. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc. Natl. Acad. Sci. USA 101:9085–9090.
   PubMed Web of Science ®Google Scholar
• Wera, S., A. Fernandez, N. J. Lamb, P. Turowski, M. Hemmings-Mieszczak, R. E. Mayer-Jaekel, and B. A. Hemmings. 1995. Deregulation of translational control of the 65-kDa regulatory subunit (PR65 alpha) of protein phosphatase 2A leads to multinucleated cells. J. Biol. Chem. 270:21374–21381.
   PubMed Web of Science ®Google Scholar
• Yada, M., S. Hatakeyama, T. Kamura, M. Nishiyama, R. Tsunematsu, H. Imaki, N. Ishida, F. Okumura, K. Nakayama, and K. I. Nakayama. 2004. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J. 23:2116–2125.
   PubMed Web of Science ®Google Scholar
• Yan, Z., S. A. Fedorov, M. C. Mumby, and R. S. Williams. 2000. PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells. Mol. Cell. Biol. 20:1021–1029.
   PubMed Web of Science ®Google Scholar
• Yang, S. I., R. L. Lickteig, R. Estes, K. Rundell, G. Walter, and M. C. Mumby. 1991. Control of protein phosphatase 2A by simian virus 40 small-t antigen. Mol. Cell. Biol. 11:1988–1995.
   PubMedGoogle Scholar
• Yeh, E., M. Cunningham, H. Arnold, D. Chasse, T. Monteith, G. Ivaldi, W. C. Hahn, P. T. Stukenberg, S. Shenolikar, T. Uchida, C. M. Counter, J. R. Nevins, A. R. Means, and R. Sears. 2004. A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells. Nat. Cell Biol. 6:308–318.
   PubMed Web of Science ®Google Scholar
• Yu, J., A. Boyapati, and K. Rundell. 2001. Critical role for SV40 small-t antigen in human cell transformation. Virology 290:192–198.
   PubMedGoogle Scholar
• Zhao, Y., G. Boguslawski, R. S. Zitomer, and A. A. DePaoli-Roach. 1997. Saccharomyces cerevisiae homologs of mammalian B and B′ subunits of protein phosphatase 2A direct the enzyme to distinct cellular functions. J. Biol. Chem. 272:8256–8262.
   PubMedGoogle Scholar