The MDM2 gene family

Biomolecular Concepts

Volumn 5, Issue 1, 2014, Pages 9-19

  Mendoza, Michael ^a   Mandani, Garni ^a   Momand, Jamil ^a  

^a CALIFORNIA STATE UNIVERSITY   (United States)

Author keywords

evolution; oncogene; p53; RING; tumor suppressor; ubiquitylation

Indexed keywords

MDM2 PROTEIN, HUMAN; MDM4 PROTEIN, HUMAN; NUCLEAR PROTEIN; ONCOPROTEIN; PROTEIN MDM2;

ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; GENETICS; HUMAN; METABOLISM; MULTIGENE FAMILY; RING FINGER MOTIF; STRUCTURAL HOMOLOGY;

ANIMALS; HUMANS; MODELS, MOLECULAR; MULTIGENE FAMILY; NUCLEAR PROTEINS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-MDM2; RING FINGER DOMAINS; STRUCTURAL HOMOLOGY, PROTEIN;

EID: 84896749843     PISSN: 18685021     EISSN: 1868503X     Source Type: Journal    
DOI: 10.1515/bmc-2013-0027     Document Type: Review

References (82)

1. Cahilly-Snyder L, Yang-Feng T, Francke U, George DL. Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Somat Cell Mol Genet 1987; 13: 235-44.
2. Fakharzadeh SS, Rosenblum-Vos L, Murphy M, Hoffman EK, George DL. Structure and organization of amplified DNA on double minutes containing the mdm2 oncogene. Genomics 1993; 15: 283-90. (Pubitemid 23099792)
3. Fakharzadeh SS, Trusko SP, George DL. Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J 1991; 10: 1565-9. (Pubitemid 21905621)
4. Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 1992; 358: 80-3.
5. Momand J, Jung D, Wilczynski S, Niland J. The MDM2 gene amplification database. Nucleic Acids Res 1998; 26: 3453-9. (Pubitemid 28347214)
6. Araki S, Eitel JA, Batuello CN, Bijangi-Vishehsaraei K, Xie XJ, Danielpour D, Pollok KE, Boothman DA, Mayo LD. TGF-beta1-induced expression of human Mdm2 correlates with late-stage metastatic breast cancer. J Clin Invest 2010; 120: 290-302.
7. Bond GL, Hirshfield KM, Kirchhoff T, Alexe G, Bond EE, Robins H, Bartel F, Taubert H, Wuerl P, Hait W, Toppmeyer D, Offit K, Levine AJ. MDM2 SNP309 accelerates tumor formation in a gender-specific and hormone-dependent manner. Cancer Res 2006; 66: 5104-10. (Pubitemid 43844932)
8. Bond GL, Menin C, Bertorelle R, Alhopuro P, Aaltonen LA, Levine AJ. MDM2 SNP309 accelerates colorectal tumour formation in women. J Med Genet 2006; 43: 950-2. (Pubitemid 46080193)
9. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 1992; 69: 1237-45.
10. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell 1997; 88: 323-31. (Pubitemid 27131374)
11. Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53. Nature 1997; 387: 296-9. (Pubitemid 27220766)
12. Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature 1997; 387: 299-303. (Pubitemid 27220767)
13. Honda R, Tanaka H, Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 1997; 420: 25-7. (Pubitemid 28037193)
14. Wu X, Bayle JH, Olson D, Levine AJ. The p53-mdm-2 autoregulatory feedback loop. Genes Dev 1993; 7: 1126-32. (Pubitemid 23207405)
15. Barak Y, Gottlieb E, Juven-Gershon T, Oren M. Regulation of mdm2 expression by p53: alternative promoters produce transcripts with nonidentical translation potential. Genes Dev 1994; 8: 1739-49. (Pubitemid 24265781)
16. Chen CY, Oliner JD, Zhan Q, Fornace Jr AJ, Vogelstein B, Kastan MB. Interactions between p53 and MDM2 in a mammalian cell cycle checkpoint pathway. Proc Natl Acad Sci USA 1994; 91: 2684-8. (Pubitemid 24139412)
17. Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C, Reiss Y, Shiloh Y, Ziv Y. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 1998; 281: 1674-7.
18. Chehab NH, Malikzay A, Appel M, Halazonetis TD. Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes Dev 2000; 14: 278-88. (Pubitemid 30106483)
19. Chehab NH, Malikzay A, Stavridi ES, Halazonetis TD. Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage. Proc Natl Acad Sci USA 1999; 96: 13777-82.
20. Maya R, Balass M, Kim ST, Shkedy D, Leal JF, Shifman O, Moas M, Buschmann T, Ronai Z, Shiloh Y, Kastan MB, Katzir E, Oren M. ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes Dev 2001; 15: 1067-77. (Pubitemid 32417300)
21. Mayo LD, Turchi JJ, Berberich SJ. Mdm-2 phosphorylation by DNA-dependent protein kinase prevents interaction with p53. Cancer Res 1997; 57: 5013-6. (Pubitemid 27498111)
22. Shieh SY, Ikeda M, Taya Y, Prives C. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 1997; 91: 325-34. (Pubitemid 27467963)
23. Shinozaki T, Nota A, Taya Y, Okamoto K. Functional role of Mdm2 phosphorylation by ATR in attenuation of p53 nuclear export. Oncogene 2003; 22: 8870-80. (Pubitemid 38021503)
24. Sionov RV, Coen S, Goldberg Z, Berger M, Bercovich B, Ben-Neriah Y, Ciechanover A, Haupt Y. c-Abl regulates p53 levels under normal and stress conditions by preventing its nuclear export and ubiquitination. Mol Cell Biol 2001; 21: 5869-78. (Pubitemid 32737804)
25. Li M, Luo J, Brooks CL, Gu W. Acetylation of p53 inhibits its ubiquitination by Mdm2. J Biol Chem 2002; 277: 50607-11. (Pubitemid 36042220)
26. Zhang Y, Xiong Y, Yarbrough WG. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 1998; 92: 725-34. (Pubitemid 28155312)
27. Kamijo T, Weber JD, Zambetti G, Zindy F, Roussel MF, Sherr CJ. Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2. Proc Natl Acad Sci USA 1998; 95: 8292-7. (Pubitemid 28326106)
28. Roth J, Dobbelstein M, Freedman DA, Shenk T, Levine AJ. 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 1998; 17: 554-64. (Pubitemid 28045495)
29. Wang X, Jiang X. Mdm2 and MdmX partner to regulate p53. FEBS Lett 2012; 586: 1390-6.
30. Kruse JP, Gu W. MSL2 promotes Mdm2-independent cytoplasmic localization of p53. J Biol Chem 2009; 284: 3250-63.
31. Sherr CJ, Weber JD. The ARF/p53 pathway. Curr Opin Genet Dev 2000; 10: 94-9. (Pubitemid 30113711)
32. Marine JC, Jochemsen AG. Mdmx as an essential regulator of p53 activity. Biochem Biophys Res Commun 2005; 331: 750-60. (Pubitemid 40615506)
33. Leng RP, Lin Y, Ma W, Wu H, Lemmers B, Chung S, Parant JM, Lozano G, Hakem R, Benchimol S. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell 2003; 112: 779-91. (Pubitemid 36378882)
34. Dornan D, Wertz I, Shimizu H, Arnott D, Frantz GD, Dowd P, O'Rourke K, Koeppen H, Dixit VM. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature 2004; 429: 86-92. (Pubitemid 38620556)
35. Shvarts A, Steegenga WT, Riteco N, van Laar T, Dekker P, Bazuine M, van Ham RC, van der Houven van Oordt W, Hateboer G, van der Eb AJ, Jochemsen AG. MDMX: a novel p53-binding protein with some functional properties of MDM2. EMBO J 1996; 15: 5349-57. (Pubitemid 26336217)
36. Toledo F, Wahl GM. Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer 2006; 6: 909-23. (Pubitemid 44862676)
37. Laurie NA, Donovan SL, Shih CS, Zhang J, Mills N, Fuller C, Teunisse A, Lam S, Ramos Y, Mohan A, Johnson D, Wilson M, Rodriguez-Galindo C, Quarto M, Francoz S, Mendrysa SM, Guy RK, Marine JC, Jochemsen AG, Dyer MA. Inactivation of the p53 pathway in retinoblastoma. Nature 2006; 444: 61-6. (Pubitemid 44684754)
38. Momand J, Aspuria PJ, Furuta S. MDM2 and MDMX regulators of p53 activity. In: Zambetti GP, editor. The p53 tumor suppressor pathway and cancer. protein reviews. New York: Springer 2005: 155-85.
39. Kamal A, Mohammed AA, Shaik TB. p53-Mdm2 inhibitors: patent review (2009-2010). Expert Opin Ther Pat 2012; 22: 95-105.
40. Pei D, Zhang Y, Zheng J. Regulation of p53: a collaboration between Mdm2 and Mdmx. Oncotarget 2012; 3: 228-35.
41. Vassilev LT. MDM2 inhibitors for cancer therapy. Trends Mol Med 2007; 13: 23-31. (Pubitemid 46027725)
42. Tanimura S, Ohtsuka S, Mitsui K, Shirouzu K, Yoshimura A, Ohtsubo M. MDM2 interacts with MDMX through their RING finger domains. FEBS Lett 1999; 447: 5-9. (Pubitemid 29134936)
43. Marine JC, Francoz S, Maetens M, Wahl G, Toledo F, Lozano G. Keeping p53 in check: essential and synergistic functions of Mdm2 and Mdm4. Cell Death Differ 2006; 13: 927-34.
44. Wang X, Wang J, Jiang X. MdmX protein is essential for Mdm2 protein-mediated p53 polyubiquitination. J Biol Chem 2011; 286: 23725-34.
45. Belyi VA, Ak P, Markert E, Wang H, Hu W, Puzio-Kuter A, Levine AJ. The origins and evolution of the p53 family of genes. Cold Spring Harb Perspect Biol 2010; 2: a001198.
46. Momand J, Villegas A, Belyi VA. The evolution of MDM2 family genes. Gene 2011; 486: 23-30.
47. Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem 1998; 67: 425-79. (Pubitemid 28411135)
48. Wenzel DM, Stoll KE, Klevit RE. E2s: structurally economical and functionally replete. Biochem J 2011; 433: 31-42.
49. Deshaies RJ, Joazeiro CA. RING domain E3 ubiquitin ligases. Annu Rev Biochem 2009; 78: 399-434.
50. Weissman AM. Themes and variations on ubiquitylation. Nat Rev Mol Cell Biol 2001; 2: 169-78. (Pubitemid 33675741)
51. Koegl M, Hoppe T, Schlenker S, Ulrich HD, Mayer TU, Jentsch S. A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly. Cell 1999; 96: 635-44. (Pubitemid 29122806)
52. Ozkan E, Yu H, Deisenhofer J. Mechanistic insight into the allosteric activation of a ubiquitin-conjugating enzyme by RING-type ubiquitin ligases. Proc Natl Acad Sci USA 2005; 102: 18890-5. (Pubitemid 43049537)
53. Kawai H, Lopez-Pajares V, Kim MM, Wiederschain D, Yuan ZM. RING domain-mediated interaction is a requirement for MDM2's E3 ligase activity. Cancer Res 2007; 67: 6026-30. (Pubitemid 47037481)
54. Borden KL, Boddy MN, Lally J, O'Reilly NJ, Martin S, Howe K, Solomon E, Freemont PS. The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBO J 1995; 14: 1532-41.
55. Dominguez C, Bonvin AM, Winkler GS, van Schaik FM, Timmers HT, Boelens R. Structural model of the UbcH5B/CNOT4 complex revealed by combining NMR, mutagenesis, and docking approaches. Structure 2004; 12: 633-44. (Pubitemid 38447166)
56. Shloush J, Vlassov JE, Engson I, Duan S, Saridakis V, Dhe-Paganon S, Raught B, Sheng Y, Arrowsmith CH. Structural and functional comparison of the RING domains of two p53 E3 ligases, Mdm2 and Pirh2. J Biol Chem 2011; 286: 4796-808.
57. Zheng N, Wang P, Jeffrey PD, Pavletich NP. Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases. Cell 2000; 102: 533-9.
58. Brzovic PS, Rajagopal P, Hoyt DW, King MC, Klevit RE. Structure of a BRCA1-BARD1 heterodimeric RING-RING complex. Nat Struc Biol 2001; 8: 833-7. (Pubitemid 32923599)
59. Buchwald G, van der Stoop P, Weichenrieder O, Perrakis A, van Lohuizen M, Sixma TK. Structure and E3-ligase activity of the Ring-Ring complex of polycomb proteins Bmi1 and Ring1b. EMBO J 2006; 25: 2465-74. (Pubitemid 44012229)
60. Mace PD, Linke K, Feltham R, Schumacher FR, Smith CA, Vaux DL, Silke J, Day CL. Structures of the cIAP2 RING domain reveal conformational changes associated with ubiquitin-conjugating enzyme (E2) recruitment. J Biol Chem 2008; 283: 31633-40.
61. Yi C, Deng XW. COP1-from plant photomorphogenesis to mammalian tumorigenesis. Trends Cell Biol 2005; 15: 618-25. (Pubitemid 41619426)
62. Beitel LK, Elhaji YA, Lumbroso R, Wing SS, Panet-Raymond V, Gottlieb B, Pinsky L, Trifiro MA. Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity. J Mol Endocrinol 2002; 29: 41-60. (Pubitemid 34965745)
63. Sheng Y, Laister RC, Lemak A, Wu B, Tai E, Duan S, Lukin J, Sunnerhagen M, Srisailam S, Karra M, Benchimol S, Arrowsmith CH. Molecular basis of Pirh2-mediated p53 ubiquitylation. Nat Struct Mol Biol 2008; 15: 1334-42.
64. Li Q, Lin S, Wang X, Lian G, Lu Z, Guo H, Ruan K, Wang Y, Ye Z, Han J, Lin SC. Axin determines cell fate by controlling the p53 activation threshold after DNA damage. Nat Cell Biol 2009; 11: 1128-34.
65. Duan S, Yao Z, Hou D, Wu Z, Zhu WG, Wu M. Phosphorylation of Pirh2 by calmodulin-dependent kinase II impairs its ability to ubiquitinate p53. EMBO J 2007; 26: 3062-74. (Pubitemid 47057489)
66. Kostic M, Matt T, Martinez-Yamout MA, Dyson HJ, Wright PE. Solution structure of the Hdm2 C2H2C4 RING, a domain critical for ubiquitination of p53. J Mol Biol 2006; 363: 433-50. (Pubitemid 44436256)
67. Linke K, Mace PD, Smith CA, Vaux DL, Silke J, Day CL. Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans. Cell Death Differ 2008; 15: 841-8. (Pubitemid 351524426)
68. Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 1987; 4: 406-25.
69. Fang S, Jensen JP, Ludwig RL, Vousden KH, Weissman AM. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem 2000; 275: 8945-51. (Pubitemid 30180252)
70. Honda R, Yasuda H. Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase. Oncogene 2000; 19: 1473-6. (Pubitemid 30171179)
71. Singh RK, Iyappan S, Scheffner M. Hetero-oligomerization with MdmX rescues the ubiquitin/Nedd8 ligase activity of RING finger mutants of Mdm2. J Biol Chem 2007; 282: 10901-7. (Pubitemid 47100746)
72. Peitsch MC. Protein modeling by e-mail. Bio/Technology 1995; 13: 658-60.
73. Arnold K, Bordoli L, Kopp J, Schwede T. The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 2006; 22: 195-201. (Pubitemid 43205406)
74. Kiefer F, Arnold K, Kunzli M, Bordoli L, Schwede T. The SWISS-MODEL Repository and associated resources. Nucleic Acids Res 2009; 37: D387-92.
75. Dehal P, Boore JL. Two rounds of whole genome duplication in the ancestral vertebrate. PLoS Biol 2005; 3: e314.
76. Kasahara M. The 2R hypothesis: an update. Curr Opin Immunol 2007; 19: 547-52. (Pubitemid 47464919)
77. Ohno S. Evolution by gene duplication. New York: Springer-Verlag, 1970.
78. Lane DP, Madhumalar A, Lee AP, Tay BH, Verma C, Brenner S, Venkatesh B. Conservation of all three p53 family members and Mdm2 and Mdm4 in the cartilaginous fish. Cell Cycle 2011; 10: 4272-9.
79. Poyurovsky MV, Priest C, Kentsis A, Borden KL, Pan ZQ, Pavletich N, Prives C. The Mdm2 RING domain C-terminus is required for supramolecular assembly and ubiquitin ligase activity. EMBO J 2007; 26: 90-101. (Pubitemid 46094702)
80. Budhidarmo R, Nakatani Y, Day CL. RINGs hold the key to ubiquitin transfer. Trends Biochem Sci 2012; 37: 58-65.
81. Goujon M, McWilliam H, Li W, Valentin F, Squizzato S, Paern J, Lopez R. A new bioinformatics analysis tools framework at EMBL-EBI. Nucleic Acids Res 2010; 38: W695-9.
82. Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H, Remmert M, Söding J, Thompson JD, Higgins DG. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 2011; 7: 539.