MDM2, An Introduction

Molecular Cancer Research

Volumn 1, Issue 14, 2003, Pages 993-1000

  Iwakuma, Tomoo ^a   Lozano, Guillermina ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARF PROTEIN; PROTEIN P53; UBIQUITIN PROTEIN LIGASE; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG;

APOPTOSIS; CANCER GENETICS; CELL CYCLE; FEEDBACK SYSTEM; GENE; GENE AMPLIFICATION; GENE DELETION; GENE EXPRESSION; GENE FUNCTION; GENE INTERACTION; GENE MUTATION; GENE STRUCTURE; GENETIC CODE; HUMAN; MURINE DOUBLE MINUTE 2 GENE; NONHUMAN; NUCLEOLUS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN MOTIF; REGULATORY MECHANISM; REVIEW; STRUCTURE ANALYSIS; TUMOR SUPPRESSOR GENE;

ANIMALS; GENE EXPRESSION REGULATION; HUMANS; NUCLEAR PROTEINS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-MDM2; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEIN P53;

ANIMALIA; MURINAE; RODENTIA;

EID: 0347716455     PISSN: 15417786     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (120)

1. Fakharzadeh, S. S., Trusko, S. P., and George, D. L. Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J., 10: 1565-1569, 1991.
2. Cahilly-Snyder, L., Yang-Feng, T., Francke, U., and George, D. L. Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Somatic Cell Mol. Genet., 13: 235-244, 1987.
3. Momand, J., Zambetti, G. P., Olson, D. C., George, D., and Levine, A. J. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell, 69: 1237-1245, 1992.
4. Oliner, J. D., Kinzler, K. W., Meltzer, P. S., George, D. L., and Vogelstein, B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature, 358: 80-83, 1992.
5. Haupt, Y., Maya, R., Kazaz, A., and Oren, M. Mdm2 promotes the rapid degradation of p53. Nature, 387: 296-299, 1997.
6. Honda, R., Tanaka, H., and Yasuda, H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett., 420: 25-27, 1997.
7. Kubbutat, M. H., Jones, S. N., and Vousden, K. H. Regulation of p53 stability by Mdm2. Nature, 387: 299-303, 1997.
8. Lee, J. C. and Peter, M. E. Regulation of apoptosis by ubiquitination. Immunol. Rev., 193: 39-47, 2003.
9. Yang, Y. and Yu, X. Regulation of apoptosis: the ubiquitous way. FASEB J., 17: 790-799, 2003.
10. Nakamura, S., Roth, J. A., and Mukhopadhyay, T. Multiple lysine mutations in the C-terminal domain of p53 interfere with MDM2-dependent protein degradation and ubiquitination. Mol. Cell. Biol., 20: 9391-9398, 2000.
11. Rodriguez, M. S., Desterro, J. M., Lain, S., Lane, D. P., and Hay, R. T. Multiple C-terminal lysine residues target p53 for ubiquitin-proteasome-mediated degradation. Mol. Cell. Biol., 20: 8458-8467, 2000.
12. Fang, S., Jensen, J. P., Ludwig, R. L., Vousden, K. H., and Weissman, A. M. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J. Biol. Chem., 275: 8945-8951, 2000.
13. Honda, R. and Yasuda, H. Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase. Oncogene, 19: 1473-1476, 2000.
14. Lai, Z., Ferry, K. V., Diamond, M. A., Wee, K. E., Kim, Y. B., Ma, J., Yang, T., Benfield, P. A., Copeland, R. A., and Auger, K. R. Human mdm2 mediates multiple mono-ubiquitination of p53 by a mechanism requiring enzyme isomerization. J. Biol. Chem., 276: 31357-31367, 2001.
15. Thrower, J. S., Hoffman, L., Rechsteiner, M., and Pickart, C. M. Recognition of the polyubiquitin proteolytic signal. EMBO J., 19: 94-102, 2000.
16. Jones, S. N., Roe, A. E., Donehower, L. A., and Bradley, A. Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature, 378: 206-208, 1995.
17. Montes de Oca Luna, R., Wagner, D. S., and Lozano, G. Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature, 378: 203-206, 1995.
18. Mendrysa, S. M., McElwee, M. K., Michalowski, J., O'Leary, K. A., Young, K. M., and Perry, M. E. mdm2 is critical for inhibition of p53 during lymphopoiesis and the response to ionizing irradiation. Mol. Cell. Biol., 23: 462-472, 2003.
19. Moll, U. M. and Petrenko, O. The MDM2-p53 Interaction. Mol. Cancer Res., 1: 1001-1008.
20. Olson, D. C., Marechal, V., Momand, J., Chen, J., Romocki, C., and Levine, A. J. Identification and characterization of multiple mdm-2 proteins and mdm-2-p53 protein complexes. Oncogene, 8: 2353-2360, 1993.
21. Saucedo, L. J., Myers, C. D., and Perry, M. E. Multiple murine double minute gene 2 (MDM2) proteins are induced by ultraviolet light. J. Biol. Chem., 274: 8161-8168, 1999.
22. Perry, M. E., Piette, J., Zawadzki, J. A., Harvey, D., and Levine, A. J. The mdm-2 gene is induced in response to UV light in a p53-dependent manner. Proc. Natl. Acad. Sci. USA, 90: 11623-11627, 1993.
23. Bartel, F., Taubert, H., and Harris, L. C. Alternative and aberrant splicing of MDM2 mRNA in human cancer. Cancer Cell, 2: 9-15, 2002.
24. Evans, S. C., Viswanathan, M., Grier, J. D., Narayana, M., El-Naggar, A. K., and Lozano, G. An alternatively spliced HDM2 product increases p53 activity by inhibiting HDM2. Oncogene, 20: 4041-4049, 2001.
25. Dang, J., Kuo, M. L., Eischen, C. M., Stepanova, L., Sherr, C. J., and Roussel, M. F. The RING domain of Mdm2 can inhibit cell proliferation. Cancer Res., 62: 1222-1230, 2002.
26. Roth, J., Dobbelstein, M., Freedman, D. A., Shenk, T., and Levine, A. J. 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, 1998.
27. Freedman, D. A. and Levine, A. J. Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6. Mol. Cell. Biol., 18: 7288-7293, 1998.
28. Lohrum, M. A., Ashcroft, M., Kubbutat, M. H., and Vousden, K. H. Identification of a cryptic nucleolar-localization signal in MDM2. Nat. Cell Biol., 2: 179-181, 2000.
29. Argentini, M., Barboule, N., and Wasylyk, B. The contribution of the acidic domain of MDM2 to p53 and MDM2 stability. Oncogene, 20: 1267-1275, 2001.
30. Zhu, Q., Yao, J., Wani, G., Wani, M. A., and Wani, A. A. Mdm2 mutant defective in binding p300 promotes ubiquitination but not degradation of p53: evidence for the role of p300 in integrating ubiquitination and proteolysis. J. Biol. Chem., 276: 29695-29701, 2001.
31. Barak, Y., Juven, T., Haffner, R., and Oren, M. mdm2 expression is induced by wild type p53 activity. EMBO J., 12: 461-468, 1993.
32. Meek, D. W. and Knippschild, U. Posttranslational Modification of MDM2. Mol. Cancer Res., 1: 1017-1026.
33. Deb, S. P. Cell Cyle Regulatory Functions of the Human Onconprotein MDM2. Mol. Cancer Res., 1: 1009-1016.
34. Ganguli, G. and Wasylyk, B. p53-Independent Functions of MDM2. Mol. Cancer Res., 1: 1027-1035.
35. Kamijo, T., Weber, J. D., Zambetti, G., Zindy, F., Roussel, M. F., and Sherr, C. J. Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2. Proc. Natl. Acad. Sci. USA, 95: 8292-8297, 1998.
36. Honda, R. and Yasuda, H. Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53. EMBO J., 18: 22-27, 1999.
37. Zhang, Y., Xiong, Y., and Yarbrough, W. G. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell, 92: 725-734, 1998.
38. Quelle, D. E., Zindy, F., Ashmun, R. A., and Sherr, C. J. Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell, 83: 993-1000, 1995.
39. Tao, W. and Levine, A. J. Nucleocytoplasmic shuttling of oncoprotein Hdm2 is required for Hdm2-mediated degradation of p53. Proc. Natl. Acad. Sci. USA, 96: 3077-3080, 1999.
40. Tao, W. and Levine, A. J. P19(ARF) stabilizes p53 by blocking nucleocytoplasmic shuttling of Mdm2. Proc. Natl. Acad. Sci. USA, 96: 6937-6941, 1999.
41. Weber, J. D., Taylor, L. J., Roussel, M. F., Sherr, C. J., and Bar-Sagi, D. Nucleolar Arf sequesters Mdm2 and activates p53. Nat. Cell Biol., 1: 20-26, 1999.
42. Zhang, Y. and Xiong, Y. Mutations in human ARF exon 2 disrupt its nucleolar localization and impair its ability to block nuclear export of MDM2 and p53. Mol. Cell, 3: 579-591, 1999.
43. Kamijo, T., Zindy, F., Roussel, M. F., Quelle, D. E., Downing, J. R., Ashmun, R. A., Grosveld, G., and Sherr, C. J. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell, 91: 649-659, 1997.
44. Midgley, C. A., Desterro, J. M., Saville, M. K., Howard, S., Sparks, A., Hay, R. T., and Lane, D. P. An N-terminal p14ARF peptide blocks Mdm2-dependent ubiquitination in vitro and can activate p53 in vivo. Oncogene, 19: 2312-2323, 2000.
45. Llanos, S., Clark, P. A., Rowe, J., and Peters, G. Stabilization of p53 by p14ARF without relocation of MDM2 to the nucleolus. Nat, Cell Biol., 3: 445-452, 2001.
46. Lohrum, M. A., Ludwig, R. L., Kubbutat, M. H., Hanlon, M., and Vousden, K. H. Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell, 3: 577-587, 2003.
47. Chen, D., Li, M., Luo, J., and Gu, W. Direct interactions between HIF-1α and Mdm2 modulate p53 function. J. Biol. Chem., 278: 13595-13598, 2003.
48. Khosravi, R., Maya, R., Gottlieb, T., Oren, M., Shiloh, Y., and Shkedy, D. Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proc. Natl. Acad. Sci. USA, 96: 14973-14977, 1999.
49. de Toledo, S. M., Azzam, E. I., Dahlberg, W. K., Gooding, T. B., and Little, J. B. ATM complexes with HDM2 and promotes its rapid phosphorylation in a p53-independent manner in normal and tumor human cells exposed to ionizing radiation. Oncogene, 19: 6185-6193, 2000.
50. Maya, R., Balass, M., Kim, S. T., Shkedy, D., Leal, J. F., Shifman, O., Moas, M., Buschmann, T., Ronai, Z., Shiloh, Y., Kastan, M. B., Katzir, E., and Oren, M. ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes Dev., 15: 1067-1077, 2001.
51. Zhou, B. P., Liao, Y., Xia, W., Zou, Y., Spohn, B., and Hung, M. C. HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat. Cell Biol, 3: 973-982, 2001.
52. Ogawara, Y., Kishishita, S., Obata, T., Isazawa, Y., Suzuki, T., Tanaka, K., Masuyama, N., and Gotoh, Y. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J. Biol. Chem., 277: 21843-21850, 2002.
53. Ashcroft, M., Ludwig, R. L., Woods, D. B., Copeland, T. D., Weber, H. O., MacRae, E. J., and Vousden, K. H. Phosphorylation of HDM2 by Akt. Oncogene, 21: 1955-1962, 2002.
54. Mayo, L. D. and Donner, D. B. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc. Natl. Acad. Sci. USA, 98: 11598-11603, 2001.
55. Sionov, R. V., Moallem, E., Berger, M., Kazaz, A., Gerlitz, O., Ben-Neriah, Y., Oren, M., and Haupt, Y. c-Abl neutralizes the inhibitory effect of Mdm2 on p53. J. Biol. Chem., 274: 8371-8374, 1999.
56. Sionov, R. V., Coen, S., Goldberg, Z., Berger, M., Bercovich, B., Ben-Neriah, Y., Ciechanover, A., and Haupt, Y. c-Abl regulates p53 levels under normal and stress conditions by preventing its nuclear export and ubiquitination. Mol. Cell. Biol., 21: 5869-5878, 2001.
57. Goldberg, Z., Vogt Sionov, R., Berger, M., Zwang, Y., Perets, R., Van Etten, R. A., Oren, M., Taya, Y., and Haupt, Y. Tyrosine phosphorylation of Mdm2 by c-Abl: implications for p53 regulation. EMBO J., 21: 3715-3727, 2002.
58. Okamoto, K., Li, H., Jensen, M. R., Zhang, T., Taya, Y., Thorgeirsson, S. S., and Prives, C. Cyclin G recruits PP2A to dephosphorylate Mdm2. Mol. Cell, 9: 761-771, 2002.
59. Chen, X. Cyclin G: a regulator of the p53-Mdm2 network. Dev. Cell, 2: 518-519, 2002.
60. Kimura, S. H. and Nojima, H. Cyclin G1 associates with MDM2 and regulates accumulation and degradation of p53 protein. Genes Cells, 7: 869-880, 2002.
61. Grossman, S. R., Perez, M., Kung, A. L., Joseph, M., Mansur, C., Xiao, Z. X., Kumar, S., Howley, P. M., and Livingston, D. M. p300/MDM2 complexes participate in MDM2-mediated p53 degradation. Mol. Cell, 2: 405-415, 1998.
62. Kawai, H., Nie, L., Wiederschain, D., and Yuan, Z. M. Dual role of p300 in the regulation of p53 stability. J. Biol. Chem., 276: 45928-45932, 2001.
63. Grossman, S. R., Deato, M. E., Brignone, C., Chan, H. M., Kung, A. L., Tagami, H., Nakatani, Y., and Livingston, D. M. Polyubiquitination of p53 by a ubiquitin ligase activity of p300. Science, 300: 342-344, 2003.
64. Shikama, N., Lee, C. W., France, S., Delavaine, L., Lyon, J., Krstic-Demonacos, M., and La Thangue, N. B. A novel cofactor for p300 that regulates the p53 response. Mol. Cell, 4: 365-376, 1999.
65. Zeng, S. X., Jin, Y., Kuninger, D. T., Rotwein, P., and Lu, H. The acetylase activity of p300 is dispensable for MDM2 stabilization. J. Biol. Chem., 278: 7453-7458, 2003.
66. Li, L., Liao, J., Ruland, J., Mak, T. W., and Cohen, S. N. ATSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control. Proc. Natl. Acad. Sci. USA, 98: 1619-1624, 2001.
67. Ruland, J., Sirard, C., Elia, A., MacPherson, D., Wakeham, A., Li, L., de la Pompa, J. L., Cohen, S. N., and Mak, T. W. p53 accumulation, defective cell proliferation, and early embryonic lethality in mice lacking tsg101. Proc. Natl. Acad. Sci. USA, 98: 1859-1864, 2001.
68. Buschmann, T., Fuchs, S. Y., Lee, C. G., Pan, Z. Q., and Ronai, Z. SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53. Cell, 101: 753-762, 2000.
69. Buschmann, T., Lerner, D., Lee, C. G., and Ronai, Z. 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, 2001.
70. Fuchs, S. Y., Lee, C. G., Pan, Z. Q., and Ronai, Z. SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53. Cell, 110: 531, 2002.
71. Gotz, C., Kartarius, S., Scholtes, P., Nastainczyk, W., and Montenarh, M. Identification of a CK2 phosphorylation site in mdm2. Eur. J. Biochem., 266: 493-501, 1999.
72. Hjerrild, M., Milne, D., Dumaz, N., Hay, T., Issinger, O. G., and Meek, D. Phosphotylation of murine double minute clone 2 (MDM2) protein at serine-267 by protein kinase CK2 in vitro and in cultured cells. Biochem. J., 355: 347-356, 2001.
73. Xiao, Z. X., Chen, J., Levine, A. J., Modjtahedi, N., Xing, J., Sellers, W. R., and Livingston, D. M. Interaction between the retinoblastoma protein and the oncoprotein MDM2. Nature, 375: 694-698, 1995.
74. Hsieh, J. K., Chan, F. S., O'Connor, D. J., Mittnacht, S., Zhong, S., and Lu, X. RB regulates the stability and the apoptotic function of p53 via MDM2. Mol. Cell, 3: 181-193, 1999.
75. Johnson-Pais, T., Degnin, C., and Thayer, M. J. pRB induces Sp1 activity by relieving inhibition mediated by MDM2. Proc. Natl. Acad. Sci. USA, 98: 2211-2216, 2001.
76. Guo, C. S., Degnin, C., Fiddler, T. A., Stauffer, D., and Thayer, M. J. Regulation of MyoD activity and muscle cell differentiation by MDM2, pRb, and Sp1. J. Biol. Chem., 278: 22615-22622, 2003.
77. Martin, K., Trouche, D., Hagemeier, C., Sorensen, T. S., La Thangue, N. B., and Kouzarides, T. Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein. Nature, 375: 691-694, 1995.
78. Loughran, O. and La Thangue, N. B. Apoptotic and growth-promoting activity of E2F modulated by MDM2. Mol. Cell. Biol., 20: 2186-2197, 2000.
79. Gu, W. and Roeder, R. G. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell, 90: 595-606, 1997.
80. Wadgaonkar, R. and Collins, T. Murine double minute (MDM2) blocks p53-coactivator interaction, a new mechanism for inhibition of p53-dependent gene expression. J. Biol. Chem., 274: 13760-13767, 1999.
81. Kobet, E., Zeng, X., Zhu, Y., Keller, D., and Lu, H. MDM2 inhibits p300-mediated p53 acetylation and activation by forming a ternary complex with the two proteins. Proc. Natl. Acad. Sci. USA, 97: 12547-12552, 2000.
82. Lin, H. K., Wang, L., Hu, Y. C., Altuwaijri, S., and Chang, C. Phosphorylation-dependent ubiquitylation and degradation of androgen receptor by Akt require Mdm2 E3 ligase. EMBO J., 21: 4037-4048, 2002.
83. Juven-Gershon, T., Shifman, O., Unger, T., Elkeles, A., Haupt, Y., and Oren, M. The Mdm2 oncoprotein interacts with the cell fate regulator Numb. Mol. Cell. Biol., 18: 3974-3982, 1998.
84. Yogosawa, S., Miyauchi, Y., Honda, R., Tanaka, H., and Yasuda, H. Mammalian Numb is a target protein of Mdm2, ubiquitin ligase. Biochem. Biophys. Res. Commun., 302: 869-872, 2003.
85. Marechal, V., Elenbaas, B., Piette, J., Nicolas, J. C., and Levine, A. J. The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes. Mol. Cell. Biol., 14: 7414-7420, 1994.
86. Elenbaas, B., Dobbelstein, M., Roth, J., Shenk, T., and Levine, A. J. The MDM2 oncoprotein binds specifically to RNA through its RING finger domain. Mol. Med., 2: 439-451, 1996.
87. Guerra, B. and Issinger, O. G. p53 and the ribosomal protein L5 participate in high molecular mass complex formation with protein kinase CK2 in murine teratocarcinoma cell line F9 after serum stimulation and cisplatin treatment. FEBS Lett., 434: 115-120, 1998.
88. Yin, Y., Stephen, C. W., Luciani, M. G., and Fahraeus, R. p53 stability and activity is regulated by Mdm2-mediated induction of alternative p53 translation products. Nat. Cell Biol., 4: 462-467, 2002.
89. Jin, Y., Zeng, S. X., Dai, M. S., Yang, X. J., and Lu, H. MDM2 inhibits PCAF (p300/CREB-binding protein-associated factor)-mediated p53 acetylation. J. Biol. Chem., 277: 30838-30843, 2002.
90. Ito, A., Kawaguchi, Y., Lai, C. H., Kovacs, J. J., Higashimoto, Y., Appella, E., and Yao, T. P. MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation. EMBO J., 21: 6236-6245, 2002.
91. Chen, J., Marechal, V., and Levine, A. J. Mapping of the p53 and mdm-2 interaction domains. Mol. Cell. Biol., 13: 4107-4114, 1993.
92. Haines, D. S., Landers, J. E., Engle, L. J., and George, D. L. Physical and functional interaction between wild-type p53 and mdm2 proteins. Mol. Cell. Biol., 14: 1171-1178, 1994.
93. Balint, E., Bates, S., and Vousden, K. H. Mdm2 binds p73α without targeting degradation. Oncogene, 18: 3923-3929, 1999.
94. Dobbelstein, M., Wienzek, S., Konig, C., and Roth, J. Inactivation of the p53-homologue p73 by the mdm2-oncoprotein. Oncogene, 18: 2101-2106, 1999.
95. Ongkeko, W. M., Wang, X. Q., Siu, W. Y., Lau, A. W., Yamashita, K., Harris, A. L., Cox, L. S., and Poon, R. Y. MDM2 and MDMX bind and stabilize the p53-related protein p73. Curr. Biol., 9: 829-832, 1999.
96. Zeng, X., Chen, L., Jost, C. A., Maya, R., Keller, D., Wang, X., Kaelin, W. G., Jr., Oren, M., Chen, J., and Lu, H. MDM2 suppresses p73 function without promoting p73 degradation. Mol. Cell. Biol., 19: 3257-3266, 1999.
97. Calabro, V., Mansueto, G., Parisi, T., Vivo, M., Calogero, R. A., and La Mantia, G. The human MDM2 oncoprotein increases the transcriptional activity and the protein level of the p53 homolog p63. J. Biol. Chem., 277: 2674-2681, 2002.
98. Boyd, M. T., Vlatkovic, N., and Haines, D. S. A novel cellular protein (MTBP) binds to MDM2 and induces a G1 arrest that is suppressed by MDM2. J. Biol. Chem., 275: 31883-31890, 2000.
99. Wei, X., Yu, Z. K., Ramalingam, A., Grossman, S. R., Yu, J. H., Bloch, D. B., and Maki, C. G. Physical and functional interactions between PML and MDM2. J. Biol. Chem., 278: 29288-29297, 2003.
100. Thut, C. J., Goodrich, J. A., and Tjian, R. Repression of p53-mediated transcription by MDM2: a dual mechanism. Genes Dev., 11: 1974-1986, 1997.
101. Leveillard, T. and Wasylyk, B. The MDM2 C-terminal region binds to TAF11250 and is required for MDM2 regulation of the cyclin A promoter. J. Biol. Chem., 272: 30651-30661, 1997.
102. Wasylyk, C. and Wasylyk, B. Defect in the p53-Mdm2 autoregulatory loop resulting from inactivation of TAF(11)250 in cell cycle mutant tsBN462 cells. Mol. Cell. Biol., 20: 5554-5570, 2000.
103. Vlatkovic, N., Guerrera, S., Li, Y., Linn, S., Haines, D. S., and Boyd, M. T. MDM2 interacts with the C-terminus of the catalytic subunit of DNA polymerase e. Nucleic Acids Res., 28: 3581-3586, 2000.
104. Asahara, H., Li, Y., Fuss, J., Haines, D. S., Vlatkovic, N., Boyd, M. T., and Linn, S. Stimulation of human DNA polymerase ε by MDM2. Nucleic Acids Res., 31: 2451-2459, 2003.
105. Shvarts, A., Steegenga, W. T., Riteco, N., van Laar, T., Dekker, P., Bazuine, M., van Ham, R. C., van der Houven van Oordt, W., Hateboer, G., van der Eb, A. J., and Jochemsen, A. G. MDMX: a novel p53-binding protein with some functional properties of MDM2. EMBO J., 15: 5349-5357, 1996.
106. Parant, J., Chavez-Reyes, A., Little, N. A., Yan, W., Reinke, V., Jochemsen, A. G., and Lozano, G. Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53. Nat. Genet., 29: 92-95, 2001.
107. Finch, R. A., Donoviel, D. B., Potter, D., Shi, M., Fan, A., Freed, D. D., Wang, C. Y., Zambrowicz, B. P., Ramirez-Solis, R., Sands, A. T., and Zhang, N. mdmx is a negative regulator of p53 activity in vivo. Cancer Res., 62: 3221-3225, 2002.
108. Migliorini, D., Denchi, E. L., Danovi, D., Jochemsen, A., Capillo, M., Gobbi, A., Helin, K., Pelicci, P. G., and Marine, J. C. Mdm4 (Mdmx) regulates p53-induced growth arrest and neuronal cell death during early embryonic mouse development. Mol. Cell. Biol., 22: 5527-5538, 2002.
109. Riemenschneider, M. J., Buschges, R., Wolter, M., Reifenberger, J., Bostrom, J., Kraus, J. A., Schlegel, U., and Reifenberger, G. Amplification and overexpression of the MDM4 (MDMX) gene from 1q32 in a subset of malignant gliomas without TP53 mutation or MDM2 amplification. Cancer Res., 59: 6091-6096, 1999.
110. Riemenschneider, M. J., Knobbe, C. B., and Reifenberger, G. Refined mapping of 1q32 amplicons in malignant gliomas confirms MDM4 as the main amplification target. Int. J. Cancer, 104: 752-757, 2003.
111. Nikolaev, A. Y., Li, M., Puskas, N., Qin, J., and Gu, W. Parc: a cytoplasmic anchor for p53. Cell, 112: 29-40, 2003.
112. Leng, R. P., Lin, Y., Ma, W., Wu, H., Lemmers, B., Chung, S., Parant, J. M., Lozano, G., Hakem, R., and Benchimol, S. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell, 112: 779-791, 2003.
113. Bernal, J. A., Luna, R., Espina, A., Lazaro, I., Ramos-Morales, F., Romero, F., Arias, C., Silva, A., Tortolero, M., and Pintor-Toro, J. A. Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis. Nat. Genet., 32: 306-311, 2002.
114. Tanimura, S., Ohtsuka, S., Mitsui, K., Shirouzu, K., Yoshimura, A., and Ohtsubo, M. MDM2 interacts with MDMX through their RING finger domains. FEBS Lett., 447: 5-9, 1999.
115. Sharp, D. A., Kratowicz, S. A., Sank, M. J., and George, D. L. Stabilization of the MDM2 oneoprotein by interaction with the structurally related MDMX protein. J. Biol. Chem., 274: 38189-38196, 1999.
116. Jackson, M. W. and Berberich, S. J. MdmX protects p53 from Mdm2-mediated degradation. Mol. Cell. Biol., 20: 1001-1007, 2000.
117. Stad, R., Little, N. A., Xirodimas, D. P., Frenk, R., van der Eb, A. J., Lane, D. P., Saville, M. K., and Jochemsen, A. G. Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms. EMBO Rep., 2: 1029-1034, 2001.
118. Stad, R., Ramos, Y. F., Little, N., Grivell, S., Attema, J., van Der Eb, A. J., and Jochemsen, A. G. Hdmx stabilizes Mdm2 and p53. J. Biol. Chem., 275: 28039-28044, 2000.
119. Migliorini, D., Danovi, D., Colombo, E., Carbone, R., Pelicci, P. G., and Marine, J. C. Hdmx recruitment into the nucleus by Hdm2 is essential for its ability to regulate p53 stability and transactivation. J. Biol. Chem., 277: 7318-7323, 2002.
120. Gu, J., Kawai, H., Nie, L., Kitao, H., Wiederschain, D., Jochemsen, A. G., Parant, J., Lozano, G., and Yuan, Z. M. Mutual dependence of MDM2 and MDMX in their functional inactivation of p53. J. Biol. Chem., 277: 19251-19254, 2002.