Functions of the MDM2 oncoprotein

Cellular and Molecular Life Sciences

Volumn 55, Issue 1, 1999, Pages 96-107

  Freedman, D A ^c   Wu, L ^a,c   Levine, A J ^b,c  

^a ROCHE MOLECULAR SYSTEMS   (United States)

^b ROCKEFELLER UNIVERSITY   (United States)

^c PRINCETON UNIVERSITY   (United States)

Author keywords

Autoregulatory feedback loop; MDM2; Oncogene; p53; Tumour suppressor

Indexed keywords

MESSENGER RNA; ONCOPROTEIN; PROTEASOME; PROTEIN MDM2; PROTEIN P53; TRANSCRIPTION FACTOR;

AMINO TERMINAL SEQUENCE; APOPTOSIS; AUTOREGULATION; CELL CYCLE G1 PHASE; CYTOPLASM; DNA DAMAGE; DNA REPAIR; FEEDBACK SYSTEM; GENE STRUCTURE; GENE TARGETING; HUMAN; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; ONCOGENE; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; ULTRAVIOLET IRRADIATION;

AMINO ACID SEQUENCE; ANIMALS; CELL CYCLE; FEEDBACK; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; NUCLEAR PROTEINS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-MDM2; SEQUENCE ALIGNMENT; TRANSCRIPTION, GENETIC; TUMOR SUPPRESSOR PROTEIN P53; VERTEBRATES;

EID: 0001837570     PISSN: 1420682X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s000180050273     Document Type: Review

References (80)

1. 1 Levine A. J. (1992) Tumor Suppressor Genes, the Cell Cycle and Cancer, Cold Spring Harbor Laboratory Press, Cold Spring Harbor
2. 2 Levine A. J., Chang A., Dittmer D., Notterman D. A., Silver A., Thorn K. et al. (1994) the p53 tumor suppressor gene. J. Lab. Clin. Med. 123: 817-823
3. 3 Chen J., Wu X., Lin J. and Levine A. J. (1996) mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein. Mol. Cell. Biol. 16: 2445-2452
4. 4 Cahilly-Snyder L., Yang-Feng T., Francke U. and George D. L. (1987) Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Som. Cell. Mol. Gen. 13: 235-244
5. 5 Fakharzadeh S. S., Trusko S. P. and George D. L. (1991) Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J. 10: 1565-1569
6. 6 Finlay C. A. (1993) The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth. Mol. Cell. Biol. 13: 301-306
7. 7 Oliner J. D., Kinzler K. W., Meltzer P. S., George D. L. and Vogelstein B. (1992) Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358: 80-83
8. 8 Meddeb M., Valent A., Danglot G., Nguyen V. C., Duverger A., Fouquet F. et al. (1996) MDM2 amplification in a primary alveolar rhabdomyosarcoma displaying a t(2;13)(q35;q14). Cytogenet. Cell. Genet. 73: 325-330
9. 9 Bueso-Ramos C. E., Yang Y., deLeon E., McCown P., Stass S. A. and Albitar M. (1993) The human MDM-2 oncogene is overexpressed in leukemias. Blood 82: 2617-2623
10. 10 Watanabe T., Hotta T., Ichikawa A., Kinoshita T., Nagai H., Uchida T. et al. (1994) The MDM2 oncogene overexpression in chronic lymphocylic leukemia and low-grade lymphoma of B-cell origin. Blood 84: 3158-3165
11. 11 Landers J. E., Haines D. S., Strauss J. F. and George D. L. (1994) Enhanced translation: a novel mechanism of mdm2 oncogene overexpression identified in human tumour cells. Oncogene 9: 2745-2750
12. 12 Landers J. E., Cassel S. L. and George D. L. (1997) Translational enhancement of mdm2 oncogene expression in human tumour cells containing a stabilized wild-type p53 protein. Cancer Res. 57: 3562-3568
13. 13 Leach F. S., Tokino T., Meltzer P., Burrell M., Oliner J. D., Smith S. et al. (1993) p53 mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res. 53: 2231-2234
14. 14 Cordon-Cardo C., Latres E., Drobnjak M., Oliva M. R., Pollack D., Woodruff J. M. et al. (1994) Molecular abnormalities of mdm-2 and P53 genes in adult soft tissue sarcomas. Cancer Res. 54: 794-799
15. 15 Ladanyi M., Cha C., Lewis R., Jhanwar S. C., Huvos A. G. and Healey J. H. (1993) MDM2 gene amplification in metastatic osteosarcoma. Cancer Res. 53: 16-18
16. 16 Lonardo F., Ueda T., Huvos A. G., Healey J. and Ladanyi M. (1997) p53 and MDM2 alterations in osteosarcomas: correlation with clinicopathologic features and proliferative rate. Cancer 79: 1541-1547
17. 17 Reifenberger G., Liu L., Ichimura K., Schmidt E. E. and Collins V. P. (1993) Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res. 53: 2736-2739
18. 18 Reifenberger G., Ichimura K., Reifenberger J., Elkahloun A. G., Meltzer P. S. and Collins V. P. (1996) Refined mapping of 12qI3-qI5 amplicons in human malignant gliomas suggests CDK4/SAS and MDM2 as independent amplification targets. Cancer Res. 56: 5141-5145
19. 19 Matsumura T., Yoshihama Y., Kimura T., Shintani S. and Alcalde R. E. (1996) p53 and MDM2 expression in oral squamous cell carcinoma. Oncology 53: 308-312
20. 20 Bueso-Ramos C. E., Manshouri T., Haidar M. A., Yang Y., McCown P., Ordonez N. et al. (1996) Abnormal expression of MDM-2 in breast carcinomas. Breast Cancer Res. Treat. 37: 179-188
21. 21 Poremba C., Yandell D. W., Metze D., Kamanabrou D., Bocker W. and Dockhorn-Dworniczak B. (1995) Immunohistochemical detection of p53 in melanomas with rare p53 gene mutations is associated with mdm-2 overexpression. Oncol. Res. 7: 331-339
22. 22 Gracia E., Fischer U., ElKahloun A., Trent J. M., Meese E. and Meltzer P. S. (1996) Isolation of genes amplified in human cancers by microdissection mediated cDNA capture. Hum. Mol. Gen. 5: 595-600
23. 23 Keleti J., Quezado M. M., Abaza M. M., Raffeld M. and Tsokos M. (1996) The MDM2 oncoprotein is overexpressed in rhabdomyosarcoma cell lines and stabilizes wild-type p53 protein. Am. J. Pathol. 149: 143-151
24. 24 Fiddler T. A., Smith L., Tapscott S. J. and Thayer M. J. (1996) Amplification of MDM2 inhibits MyoD-mediated myogenesis. Mol. Cell. Biol. 16: 5048-5057
25. 25 Corvi R., Savelyeva L., Breit S., Wenzel A., Handgretinger R., Barak J. et al. (1995) Non-syntenic amplification of MDM2 and MYCN in human neuroblastoma. Oncogene 10: 1081-1086
26. 26 He J., Reifenberger G., Liu L., Collins V. P. and James C. D. (1994) Analysis of glioma cell lines for amplification and overexpression of MDM2. Genes Chrom. Cancer 11: 91-96
27. 27 Sheikh M. S., Shao Z.-M., Hussain A. and Fontana J. A. (1993) The p53-binding protein MDM2 gene is differentially expressed in human breast carcinoma. Cancer Res. 53: 3226-3228
28. 28 Gudas J. M., Nguyen H., Klein R. C., Katayose D., Seth P. and Cowan K. H. (1995) Differential expression of multiple MDM2 messenger RNAs and proteins in normal and tumourigenic breast epithelial cells. Clin. Cancer Res. 1: 71-80
29. 29 Picksley S. M., Spicer J. F., Barnes D. M. and Lane D. P. (1996) The p53 MDM2 interaction in a cancer-prone family, and the identification of a novel therapeutic target. Acta Onc. 35: 429-434
30. 30 Lundgren K., Montes de Oca Luna R., McNeill Y. B., Emerick E. P., Spencer B., Barfield C. R. et al. (1997) Targeted expression of MDM2 uncouples S phase from mitosis and inhibits mammary gland development independent of p53. Genes Dev. 11: 714-725
31. 31 Montes de Oca Luna R., Tabor A. D., Eberspaecher H., Hulboy D. L., Worth L. L., Colman M. S. et al. (1996) The organization and expression of the mdm2 gene. Genomics 33: 352-357
32. 32 Olson D. C., Marechal V., Momand J., Chen J., Romocki C. and Levine A. J. (1993) Identification and characterization of multiple mdm-2 proteins and mdm2-p53 protein complexes. Oncogene 8: 2353-2360
33. 33 Barak Y., Gottlieb E., Juven-Gershon T. and Oren M. (1994) Regulation of mdm2 expression by p53: alternative promoters produce transcripts with nonidentical translation potential. Genes Dev. 8: 1739-1749
34. 34 Zauberman A., Flusberg D., Haupt Y., Barak Y. and Oren M. (1995) A functional p53-responsive intronic promoter is contained within the human mdm2 gene. Nucleic Acids Res. 23: 2584-2592
35. 35 Marechal V., Elenbaas B., Taneyhill L., Piette J., Mechali M., Nicolas J.-C. et al. (1997) Conservation of structural domains and biochemical activities of the MDM2 protein from Xenopus laevis. Oncogene 14: 1427-1433
36. 36 Chen J., Marechal V. and Levine A. J. (1993) Mapping of the p53 and mdm-2 interaction domains. Mol. Cell. Biol. 13: 4107-4114
37. 37 Chen J., Lin J. and Levine A. J. (1995) Regulation of transcription functions of the p53 tumor suppressor by the mdm-2 oncogene. Mol. Med. 1: 142-152
38. 38 Roth J., Dobbelstein M., Freedman D. A., Shenk T. and Levine A. J. (1998) Nucleo-cytoplasmic shuttling of the hdm2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein. EMBO J. 17: 554-564
39. 39 Marechal V., Elenbaas B., Piette J., Nicolas J.-C. and Levine A. J. (1994) The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes. Mol. Cell. Biol. 14: 7414-7420
40. 40 Erhardt P., Tomaselli K. J. and Cooper G. M. (1997) Identification of the MDM2 oncoprotein as a substrate for CPP32-like apoptotic proteascs. J. Biol. Chem. 272: 15049-15052
41. 41 Chen L., Marechal V., Moreau J., Levine A. J. and Chen J. (1997) Proteolytic cleavage of the mdm2 oncoprotein during apoptosis. J. Biol. Chem. 272: 22966-22973
42. 42 Boddy M. N., Freemont P. S. and Borden K. L. B. (1994) The p53-associated protein MDM2 contains a newly characterized zinc-binding domain called the RING finger. Trends Biochem. Sci. 19: 198-199
43. 43 Elenbaas B., Dobbelstein M., Roth J., Shenk T. and Levine A. J. (1996) The MDM2 oncoprotein binds specifically to RNA through its RING finger domain. Mol. Med. 2: 439-451
44. 44 Honda R., Tanaka H. and Yasuda H. (1997) Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 420: 25-27
45. 45 Kussie P. H., Gorina S., Marechal V., Elenbaas B., Moreau J., Levine A. J. et al. (1996) Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274: 948-953
46. 46 Uesugi M., Nyanguile O., Lu H., Levine A. J. and Verdine G. L. (1997) Induced α helix in the VP16 activation domain upon binding to a human TAF. Science 277: 1310-1313
47. 47 Freedman D. A., Epstein C. B., Roth J. C. and Levine A. J. (1997) A genetic approach to mapping the p53 binding site in the MDM2 protein. Mol. Med. 3: 248-259
48. 48 Lin J., Chen J., Elenbaas B. and Levine A. J. (1994) Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev. 8: 1235-1246
49. ∥60. Science 267: 100-104
50. ∥31 protein is a transcriptional coactivator of the p53 protein. Proc. Natl. Acad. Sci. USA 92: 5154-5158
51. 51 Kubbutat M. H. G., Jones S. N. and Vousden K. H. (1997) Regulation of p53 stability by Mdm2. Nature 387: 299-303
52. 52 Haupt Y., Maya R., Kazaz A. and Oren M. (1997) Mdm2 promotes the rapid degradation of p53. Nature 387: 296-299
53. 53 Shvarts A., Steegenga W. T., Riteco N., van Laar T., Dekker P., Bazuine M. et al. (1996) MDMX: a novel p53-binding protein with some functional properties of MDM2. EMBO J. 15: 5349-5357
54. 54 Shvarts A., Bazuine M., Dekker P., Ramos Y. F. M., Steegenga W. T., Merckx G. et al. (1997) Isolation and identification of the human homolog of a new p53-binding protein, Mdmx. Genomics 43: 34-42
55. 55 Wu X., Bayle J. H., Olson D. and Levine A. J. (1993) The p53-mdm-2 autoregulatory feedback loop. Genes Dev. 7: 1126-1132
56. 56 Barak Y., Juven T., Haffner R. and Oren M. (1993) mdm2 expression is induced by wild type p53 activity. EMBO J. 12: 461-468
57. 57 Juven T., Barak Y., Zauberman A., George D. L. and Oren M. (1993) Wild type p53 can mediate sequence-specific transactivation of an internal promoter within the mdm2 gene. Oncogene 8: 3411-3416
58. 58 Perry M. E., Piette J., Zawadzki J. A., Harvey D. and Levine A. J. (1993) The mdm-2 gene is induced in response to UV light in a p53-dependent manner. Proc. Natl. Acad. Sci. USA 90: 11623-11627
59. 59 Chen C.-Y., Oliner J. D., Zhan Q., Fornace A. J., Vogelstein B. and Kastan M. B. (1994) Interactions between p53 and MDM2 in a mammalian cell cycle checkpoint pathway. Proc. Natl. Acad. Sci. USA 91: 2684-2688
60. 60 Reinke V. and Lozano G. (1997) The p53 targets mdm2 and Fas are not required as mediated of apoptosis in vivo. Oncogene 15: 1527-1534
61. 61 Momand J., Zambetti G. P., Olson D. C., George D. and Levine A. J. (1992) The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69: 1237-1245
62. 62 Oliner J. D., Pietenpol J. A., Thiagalingam S., Gyuris J., Kinzler K. W. and Vogelstein B. (1993) Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature 362: 857-860
63. 63 Montes de Oca Luna R., Wagner D. S. and Lozano G. (1995) Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 378: 203-206
64. 64 Jones S. N., Roe A. E., Donehower L. A. and Bradley A. (1995) Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature 378: 206-208
65. 65 Thut C. J., Goodrich J. A. and Tjian R. (1997) Repression of p53-mediated transcription by MDM2: a dual mechanism. Genes Dev. 11: 1974-1986
66. 66 Shieh S.-Y., Ikeda M., Taya Y. and Prives C. (1997) DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 91: 325-334
67. 67 Lu H., Fisher R. P., Bailey P. and Levine A. J. (1997) The CDK7-cycH-p36 complex of transcription factor IIH phosphorylates p53, enhancing its sequence-specific DNA binding activity in vitro. Mol. Cell. Biol. 17: 5923-5934
68. 68 Maltznian W. and Czyzyk L. (1984) UV Irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells. Mol. Cell. Biol. 4: 1689-1694
69. 69 Wu L. and Levine A. J. (1997) Differential regulation of the p21/WAF-1 and mdm2 genes after high-dose UV irradiation: p53-dependent and p53-independent regulation of the mdm2 gene. Mol. Med. 3: 441-451
70. 70 Martin K., Trouche D., Hagemeler C., Sorensen T. S., La Thangue N. B. and Kouzarides T. (1995) Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein. Nature 375: 691-694
71. 71 Xiao Z.-X., Chen J., Levine A. J., Modjtahedl N., Xing J., Sellers W. R. et al. (1995) Interaction between the retinoblastoma protein and the oncoprotein MDM2. Nature 375: 694-698
72. 72 Böttger A., Böttger V., Sparks A., Liu W.-L., Howard S. F. and Lane D. P. (1997) Design of a synthetic Mdm2-binding mini protein that activates the p53 response in vivo. Curr. Biol. 7: 860-869
73. 73 Blaydes J. P., Gire V., Rowson J. M. and Wynford-Thomas D. (1997) Tolerance of high levels of wild-type p53 in transformed epithelial cells dependent on auto-regulation by mdm-2. Oncogene 14: 1859-1868
74. 73a Freedman D. A. and Levine A. J. (1998) Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6. Mol. Cell. Biol., in press
75. 74 Chen L., Agrawal S., Zhou W., Zhang R. and Chen J. (1998) Synergistic activation of p53 by inhibition of MDM2 expression and DNA damage. Proc. Natl. Acad. Sci. USA 95: 195-200
76. 75 Thompson J. D., Higgins D. G. and Gibson T. J. (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22: 4673-4680
77. 76 Kastan M. B., Zhan Q., El-Deiry W. S., Carrier F., Jacks T., Walsh W. V. et al. (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71: 587-597
78. 77 El-Deiry W. S., Tokino T., Velculescu V. E., Levy D. B., Parsons R., Trent J. M. et al. (1993) WAF1, a potential mediator of p53 tumor suppression. Cell 75: 817-825
79. 78 Okamoto K. and Beach D. (1994) Cyclin G is a transcriptional target of the p53 tumor suppressor protein. EMBO J. 13: 4816-4822
80. 79 Miyashita T. and Reed J. C. (1995) Tumor suppressor p53 Is a direct transcriptional activator of the human bax gene. Cell 80: 293-299