Human MDM2 isoforms translated differentially on constitutive versus p53-regulated transcripts have distinct functions in the p53/MDM2 and TSG101/MDM2 feedback control loops

Molecular and Cellular Biology

Volumn 27, Issue 1, 2007, Pages 111-119

  Cheng, Tzu Hao ^a,b   Cohen, Stanley N ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NATIONAL YANG MING UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

ADENINE; GUANINE; HYBRID PROTEIN; ISOPROTEIN; P75 MDM2 PROTEIN; P90 MDM2 PROTEIN; PROTEIN; PROTEIN MDM2; PROTEIN P53; PROTEIN P75; TUMOR SUSCEPTIBILITY GENE 101 PROTEIN; UBIQUITIN; UNCLASSIFIED DRUG; URACIL;

AMINO TERMINAL SEQUENCE; ANIMAL CELL; ARTICLE; CELL DIFFERENTIATION; CELL GROWTH; CONTROLLED STUDY; DNA SEQUENCE; FEEDBACK SYSTEM; FUNCTIONAL PROTEOMICS; HUMAN; HUMAN CELL; MOLECULAR MODEL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN SYNTHESIS; PROTEIN TRANSPORT; RNA TRANSLATION; START CODON; TRANSLATION INITIATION;

ANIMALS; CELL LINE, TUMOR; CODON; DNA-BINDING PROTEINS; FEEDBACK, BIOCHEMICAL; HUMANS; MICE; MODELS, GENETIC; PROMOTER REGIONS (GENETICS); PROTEIN BIOSYNTHESIS; PROTEIN ISOFORMS; PROTEIN STRUCTURE, TERTIARY; PROTO-ONCOGENE PROTEINS C-MDM2; RNA, MESSENGER; TRANSCRIPTION FACTORS; TUMOR SUPPRESSOR PROTEIN P53;

MURINAE;

EID: 33845803180     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.00235-06     Document Type: Article

References (59)

1. Ashcroft, M., R. L. Ludwig, D. B. Woods, T. D. Copeland, H. O. Weber, E. J. MacRae, and K. H. Vousden. 2002. Phosphorylation of HDM2 by Akt. Oncogene 21:1955-1962.
2. Barak, Y., E. Gottlieb, T. Juven-Gershon, and M. Oren. 1994. Regulation of mdm2 expression by p53: alternative promoters produce transcripts with nonidentical translation potential. Genes Dev. 8:1739-1749.
3. Barak, Y., T. Juven, R. Haffner, and M. Oren. 1993. mdm2 expression is induced by wild type p53 activity. EMBO J. 12:461-468.
4. Bartel, F., H. Taubert, and L. C. Harris. 2002. Alternative and aberrant splicing of MDM2 mRNA in human cancer. Cancer Cell 2:9-15.
5. Bond, G. L., W. Hu, and A. J. Levine. 2005. MDM2 is a central node in the p53 pathway: 12 years and counting. Curr. Cancer Drug Targets 5:3-8.
6. Buschmann, T., S. Y. Fuchs, C. G. Lee, Z. Q. Pan, and Z. Ronai. 2000. SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53. Cell 101:753-762.
7. Buschmann, T., D. Lerner, C. G. Lee, and Z. Ronai. 2001. The Mdm-2 amino terminus is required for Mdm2 binding and SUMO-1 conjugation by the E2 SUMO-1 conjugating enzyme Ubc9. J. Biol. Chem. 276:40389-40395.
8. Calkhoven, C. F., C. Muller, and A. Leutz. 2000. Translational control of C/EBPalpha and C/EBPbeta isoform expression. Genes Dev. 14:1920-1932.
9. Calkhoven, C. F., C. Muller, R. Martin, G. Krosl, H. Pietsch, T. Hoang, and A. Leutz. 2003. Translational control of SCL-isoform expression in hematopoietic lineage choice. Genes Dev. 17:959-964.
10. Chang, Y. C., Y. S. Lee, T. Tejima, K. Tanaka, S. Omura, N. H. Heintz, Y. Mitsui, and J. Magae. 1998. mdm2 and bax, downstream mediators of the p53 response, are degraded by the ubiquitin-proteasome pathway. Cell Growth Differ. 9:79-84.
11. Chen, J., V. Marechal, and A. J. Levine. 1993. Mapping of the p53 and mdm-2 interaction domains. Mol. Cell. Biol. 13:4107-4114.
12. Courtois, S., G. Verhaegh, S. North, M. G. Luciani, P. Lassus, U. Hibner, M. Oren, and P. Hainaut. 2002. DeltaN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53. Oncogene 21:6722-6728.
13. Daujat, S., H. Neel, and J. Piette. 2001. MDM2: life without p53. Trends Genet. 17:459-464.
14. Fakharzadeh, S. S., S. P. Trusko, and D. L. George. 1991. Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J. 10:1565-1569.
15. Fang, S., J. P. Jensen, R. L. Ludwig, K. H. Vousden, and A. M. Weissman. 2000. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J. Biol. Chem. 275:8945-8951.
16. Feng, G. H., C. J. Lih, and S. N. Cohen. 2000. TSG101 protein steady-state level is regulated posttranslationally by an evolutionarily conserved COOH-terminal sequence. Cancer Res. 60:1736-1741.
17. Fuchs, S. Y., C. G. Lee, Z. Q. Pan, and Z. Ronai. 2002. SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53. Cell 110:531.
18. Garrus, J. E., U. K. von Schwedler, O. W. Pornillos, S. G. Morham, K. H. Zavitz, H. E. Wang, D. A. Wettstein, K. M. Stray, M. Cote, R. L. Rich, D. G. Myszka, and W. I. Sundquist. 2001. Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell 107:55-65.
19. Haupt, Y., R. Maya, A. Kazaz, and M. Oren. 1997. Mdm2 promotes the rapid degradation of p53. Nature 387:296-299.
20. Hittelman, A. B., D. Burakov, J. A. Iniguez-Lluhi, L. P. Freedman, and M. J. Garabedian. 1999. Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins. EMBO J. 18:5380-5388.
21. Honda, R., H. Tanaka, and H. Yasuda. 1997. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 420:25-27.
22. Hsieh, J. K., F. S. Chan, D. J. O'Connor, S. Mittnacht, S. Zhong, and X. Lu. 1999. RB regulates the stability and the apoptotic function of p53 via MDM2. Mol. Cell 3:181-193.
23. Jin, X., E. Turcott, S. Englehardt, G. J. Mize, and D. R. Morris. 2003. The two upstream open reading frames of oncogene mdm2 have different translational regulatory properties. J. Biol. Chem. 278:25716-25721.
24. Jones, S. N., A. R. Hancock, H. Vogel, L. A. Donehower, and A. Bradley. 1998. Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis. Proc. Natl. Acad. Sci. USA 95:15608-15612.
25. Juven, T., Y. Barak, A. Zauberman, D. L. George, and M. Oren. 1993. Wild type p53 can mediate sequence-specific transactivation of an internal promoter within the mdm2 gene. Oncogene 8:3411-3416.
26. Kubbutat, M. H., S. N. Jones, and K. H. Vousden. 1997. Regulation of p53 stability by Mdm2. Nature 387:299-303.
27. Lahav, G., N. Rosenfeld, A. Sigal, N. Geva-Zatorsky, A. J. Levine, M. B. Elowitz, and U. Alon. 2004. Dynamics of the p53-Mdm2 feedback loop in individual cells. Nat. Genet. 36:147-150.
28. Li, L., and S. N. Cohen. 1996. Tsg101: a novel tumor susceptibility gene isolated by controlled homozygous functional knockout of allelic loci in mammalian cells. Cell 85:319-329.
29. Li, L., J. Liao, J. Ruland, T. W. Mak, and S. N. Cohen. 2001. A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control. Proc. Natl. Acad. Sci. USA 98:1619-1624.
30. Lu, Q., L. W. Hope, M. Brasch, C. Reinhard, and S. N. Cohen. 2003. TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation. Proc. Natl. Acad. Sci. USA 100:7626-7631.
31. Martin, K., D. Trouche, C. Hagemeier, T. S. Sorensen, N. B. La Thangue, and T. Kouzarides. 1995. Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein. Nature 375:691-694.
32. Martin-Serrano, J., T. Zang, and P. D. Bieniasz. 2001. HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress. Nat. Med. 7:1313-1319.
33. Mayo, L. D., and D. B. Donner. 2001. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc. Natl. Acad. Sci. USA 98:11598-11603.
34. Meek, D. W., and U. Knippschild. 2003. Posttranslational modification of MDM2. Mol. Cancer Res. 1:1017-1026.
35. Mendrysa, S. M., M. K. McElwee, and M. E. Perry. 2001. Characterization of the 5′ and 3′ untranslated regions in murine mdm2 mRNAs. Gene 264:139-146.
36. Metivier, R., G. Penot, R. P. Carmouche, M. R. Hubner, G. Reid, S. Denger, D. Manu, H. Brand, M. Kos, V. Benes, and F. Gannon. 2004. Transcriptional complexes engaged by apo-estrogen receptor-alpha isoforms have divergent outcomes. EMBO J. 23:3653-3666.
37. Miyauchi, Y., S. Yogosawa, R. Honda, T. Nishida, and H. Yasuda. 2002. Sumoylation of Mdm2 by protein inhibitor of activated STAT (PIAS) and RanBP2 enzymes. J. Biol. Chem. 277:50131-50136.
38. Moberg, K. H., S. Schelble, S. K. Burdick, and I. K. Hariharan. 2005. Mutations in erupted, the Drosophila ortholog of mammalian tumor susceptibility gene 101, elicit non-cell-autonomous overgrowth. Dev. Cell. 9:699-710.
39. Momand, J., D. Jung, S. Wilczynski, and J. Niland. 1998. The MDM2 gene amplification database. Nucleic Acids Res. 26:3453-3459.
40. Momand, J., G. P. Zambetti, D. C. Olson, D. George, and A. J. Levine. 1992. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69:1237-1245.
41. Oliner, J. D., K. W. Kinzler, P. S. Meltzer, D. L. George, and B. Vogelstein. 1992. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358:80-83.
42. Perry, M. E., S. M. Mendrysa, L. J. Saucedo, P. Tannous, and M. Holubar. 2000. p76(MDM2) inhibits the ability of p90(MDM2) to destabilize p53. J. Biol. Chem. 275:5733-5738.
43. Pochampally, R., B. Fodera, L. Chen, W. Shao, E. A. Levine, and J. Chen. 1998. A 60 kd MDM2 isoform is produced by caspase cleavage in non-apoptotic tumor cells. Oncogene 17:2629-2636.
44. Reid, G., M. R. Hubner, R. Metivier, H. Brand, S. Denger, D. Manu, J. Beaudouin, J. Ellenberg, and F. Gannon. 2003. Cyclic, proteasome-mediated turnover of unliganded and liganded ERalpha on responsive promoters is an integral feature of estrogen signaling. Mol. Cell 11:695-707.
45. Ruland, J., C. Sirard, A. Elia, D. MacPherson, A. Wakeham, L. Li, J. L. de la Pompa, S. N. Cohen, and T. W. Mak. 2001. p53 accumulation, defective cell proliferation, and early embryonic lethality in mice lacking tsg101. Proc. Natl. Acad. Sci. USA 98:1859-1864.
46. Saucedo, L. J., C. D. Myers, and M. E. Perry. 1999. Multiple murine double minute gene 2 (MDM2) proteins are induced by ultraviolet light. J. Biol. Chem. 274:8161-8168.
47. Sigalas, L, A. H. Calvert, J. J. Anderson, D. E. Neal, and J. Lunec. 1996. Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: transforming ability and frequent detection in human cancer. Nat. Med. 2:912-917.
48. Spotts, G. D., S. V. Patel, Q. Xiao, and S. R. Hann. 1997. Identification of downstream-initiated c-Myc proteins which are dominant-negative inhibitors of transactivation by full-length c-Myc proteins. Mol. Cell. Biol. 17:1459-1468.
49. Sun, P., P. Dong, K. Dai, G. J. Hannon, and D. Beach. 1998. p53-independent role of MDM2 in TGF-beta1 resistance. Science 282:2270-2272.
50. Uchida, C., S. Miwa, K. Kitagawa, T. Hattori, T. Isobe, S. Otani, T. Oda, H. Sugimura, T. Kamijo, K. Ookawa, H. Yasuda, and M. Kitagawa. 2005. Enhanced Mdm2 activity inhibits pRB function via ubiquitin-dependent degradation. EMBO J. 24:160-169.
51. Veldhoen, N., S. Metcalfe, and J. Milner. 1999. A novel exon within the mdm2 gene modulates translation initiation in vitro and disrupts the p53-binding domain of mdm2 protein. Oncogene 18:7026-7033.
52. Wagner, K. U., A. Krempler, Y. Qi, K. Park, M. D. Henry, A. A. Triplett, G. Riedlinger, I. E. Rucker, and L. Hennighausen. 2003. Tsg101 is essential for cell growth, proliferation, and cell survival of embryonic and adult tissues. Mol. Cell. Biol. 23:150-162.
53. Wu, X., J. H. Bayle, D. Olson, and A. J. Levine. 1993. The p53-mdm-2 autoregulatory feedback loop. Genes Dev. 7:1126-1132.
54. Xie, W., L. Li, and S. N. Cohen. 1998. Cell cycle-dependent subcellular localization of the TSG101 protein and mitotic and nuclear abnormalities associated with TSG101 deficiency. Proc. Natl. Acad. Sci. USA 95:1595-1600.
55. Xirodimas, D. P., J. Chisholm, J. M. Desterro, D. P. Lane, and R. T. Hay. 2002. P14ARF promotes accumulation of SUMO-1 conjugated (H)Mdm2. FEBS Lett. 528:207-211.
56. Yam, C. H., W. Y. Siu, T. Arooz, C. H. Chiu, A. Lau, X. Q. Wang, and R. Y. Poon. 1999. MDM2 and MDMX inhibit the transcriptional activity of ectopically expressed SMAD proteins. Cancer Res. 59:5075-5078.
57. Yin, Y., C. W. Stephen, M. G. Luciani, and R. Fahraeus. 2002. p53 Stability and activity is regulated by Mdm2-mediated induction of alternative p53 translation products. Nat. Cell. Biol. 4:462-467.
58. Zauberman, A., D. Fiusberg, Y. Haupt, Y. Barak, and M. Oren. 1995. A functional p53-responsive intronic promoter is contained within the human mdm2 gene. Nucleic Acids Res. 23:2584-2592.
59. Zhou, B. P., Y. Liao, W. Xia, Y. Zou, B. Spohn, and M. C. Hung. 2001. HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat. Cell. Biol. 3:973-982.