Distinct roles of MDMX in the regulation of p53 response to ribosomal stress

Cell Cycle

Volumn 6, Issue 2, 2007, Pages 151-155

  Gilkes, Daniele M ^a   Chen, Jiandong ^a  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

Author keywords

5 fluorouracil; Actinomycin D; L11; L23; L5; MDM2; MDMX; P53; Ribosomal protein

Indexed keywords

PROTEIN MDM2; PROTEIN MDMX; PROTEIN P53; RIBOSOME RNA;

BIOGENESIS; CANCER THERAPY; CELL CYCLE ARREST; CELL CYCLE PROGRESSION; CELL PROLIFERATION; CELL STRESS; DNA DAMAGE; HUMAN; NONHUMAN; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING; REVIEW; RIBOSOME; SIGNAL TRANSDUCTION;

EID: 33846937353     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.6.2.3719     Document Type: Review

References (79)

1. 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.
2. Sharp DA, Kratowicz SA, Sank MJ, George DL. Stabilization of the mdm2 oncoprotein by interaction with the structurally related mdmx protein. J Biol Chem 1999; 274:38189-96.
3. 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.
4. Marine JC, Jochemsen AG. Mdmx and mdm2: Brothers in arms? Cell Cycle 2004; 3:900-4.
5. Stad R, Little NA, Xirodimas DP, Frenk R, van der Eb AJ, Lane DP, Saville MK, Jochemsen AG. Mdmx stabilizes p53 and mdm2 via two distinct mechanisms. EMBO Rep 2001; 2:1029-34.
6. Linares LK, Hengstermann A, Ciechanover A, Muller S, Scheffner M. Hdmx stimulates hdm2-mediated ubiquitination and degradation of p53. Proc Natl Acad Sci USA 2003; 100:12009-14.
7. Gu J, Kawai H, Nie L, Kitao H, Wiederschain D, Jochemsen AG, Parant J, Lozano G, Yuan ZM. Mutual dependence of mdm2 and mdmx in their functional inactivation of p53. J Biol Chem 2002; 277:19251-4.
8. Pan Y, Chen J. Mdm2 promotes ubiquitination and degradation of mdmx. Mol Cell Biol 2003; 23:5113-21.
9. Kawai H, Wiederschain D, Kitao H, Stuart J, Tsai KK, Yuan ZM. DNA damage-induced mdmx degradation is mediated by mdm2. J Biol Chem 2003; 278:45946-53.
10. de Graaf P, Little NA, Ramos YF, Meulmeester E, Letteboer SJ, Jochemsen AG. Hdmx protein stability is regulated by the ubiquitin ligase activity of mdm2. J Biol Chem 2003; 278:38315-24.
11. Stommel JM, Wahl GM. Accelerated mdm2 auto-degradation induced by DNA-damage kinases is required for p53 activation. Embo J 2004; 23:1547-56.
12. Stommel JM, Wahl GM. A new twist in the feedback loop: Stress-activated mdm2 destabilization is required for p53 activation. Cell Cycle 2005; 4:411-7.
13. Finch RA, Donoviel DB, Potter D, Shi M, Fan A, Freed DD, Wang CY, Zambrowicz BP, Ramirez-Solis R, Sands AT, Zhang N. Mdmx is a negative regulator of p53 activity in vivo. Cancer Res 2002; 62:3221-5.
14. Migliorini D, Lazzerini Denchi E, Danovi D, Jochemsen A, Capillo M, Gobbi A, Helin K, Pelicci PG, Marine JC. Mdm4 (mdmx) regulates p53-induced growth arrest and neuronal cell death during early embryonic mouse development. Mol Cell Biol 2002; 22:5527-38.
15. Parant JM, Reinke V, Mims B, Lozano G. Organization, expression, and localization of the murine mdmx gene and pseudogene. Gene 2001; 270:277-83.
16. Grier JD, Xiong S, Elizondo-Fraire AC, Parant JM, Lozano G. Tissue-specific differences of p53 inhibition by mdm2 and mdm4. Mol Cell Biol 2006; 26:192-8.
17. Xiong S, Van Pelt CS, Elizondo-Fraire AC, Liu G, Lozano G. Synergistic roles of mdm2 and mdm4 for p53 inhibition in central nervous system development. Proc Natl Acad Sci USA 2006; 103:3226-31.
18. Maetens M, Doumont G, De Clercq S, Francoz S, Froment P, Bellefroid E, Klingmuller U, Lozano G, Marine JC. Distinct roles of mdm2 and mdm4 in red cell production. Blood 2006.
19. Francoz S, Froment P, Bogaerts S, De Clercq S, Maetens M, Doumont G, Bellefroid E, Marine JC. Mdm4 and mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells in vivo. Proc Natl Acad Sci USA 2006; 103:3232-7.
20. Danovi D, Meulmeester E, Pasini D, Migliorini D, Capra M, Frenk R, de Graaf P, Francoz S, Gasparini P, Gobbi A, Helin K, Pelicci PG, Jochemsen AG, Marine JC. Amplification of mdmx (or mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity. Mol Cell Biol 2004; 24:5835-43.
21. Ramos YF, Stad R, Attema J, Peltenburg LT, van der Eb AJ, Jochemsen AG. Aberrant expression of hdmx proteins in tumor cells correlates with wild-type p53. Cancer Res 2001; 61:1839-42.
22. Riemenschneider MJ, Buschges R, Wolter M, Reifenberger J, Bostrom J, Kraus JA, Schlegel U, 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 1999; 59:6091-6.
23. 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.
24. 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.
25. 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.
26. Shieh SY, Ahn J, Tamai K, Taya Y, Prives C. The human homologs of checkpoint kinases chkl and cds1 (chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev 2000; 14:289-300.
27. Shieh SY, Ikeda M, Taya Y, Prives C. DNA damage-induced phosphorylation of p53 alleviates inhibition by mdm2. Cell 1997; 91:325-34.
28. 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.
29. Goldberg Z, Vogt Sionov R, Berger M, Zwang Y, Perets R, Van Etten RA, Oren M, Taya Y, Haupt Y. Tyrosine phosphorylation of mdm2 by c-abl: Implications for p53 regulation. Embo J 2002; 21:3715-27.
30. Prives C, Hall PA. The p53 pathway. J Pathol 1999; 187:112-26.
31. Pereg Y, Shkedy D, de Graaf P, Meulmeester E, Edelson-Averbukh M, Salek M, Biton S, Teunisse AF, Lehmann WD, Jochemsen AG, Shiloh Y. Phosphorylation of hdmx mediates its hdm2- and atm-dependent degradation in response to DNA damage. Proc Natl Acad Sci USA 2005; 102:5056-61.
32. Chen L, Gilkes DM, Pan Y, Lane WS, Chen J. Atm and chk2-dependent phosphorylation of mdmx contribute to p53 activation after DNA damage. Embo J 2005; 24:3411-22.
33. Jin Y, Dai MS, Lu SZ, Xu Y, Luo Z, Zhao Y, Lu H. 14-3-3gamma binds to mdmx that is phosphorylated by uv-activated chk1, resulting in p53 activation. Embo J 2006; 25:1207-18.
34. LeBron C, Chen L, Gilkes DM, Chen J. Regulation of mdmx nuclear import and degradation by chk2 and 14-3-3. Embo J 2006; 25:1196-206.
35. Pereg Y, Lam S, Teunisse A, Biton S, Meulmeester E, Mittelman L, Buscemi G, Okamoto K, Taya Y, Shiloh Y, Jochemsen AG. Differential roles of atm- and chk2-mediated phosphorylations of hdmx in response to DNA damage. Mol Cell Biol 2006; 26:6819-31.
36. Meulmeester E, Maurice MM, Boutell C, Teunisse AF, Ovaa H, Abraham TE, Dirks RW, Jochemsen AG. Loss of hausp-mediated deubiquitination contributes to DNA damage-induced destabilization of hdmx and hdm2. Mol Cell 2005; 18:565-76.
37. Meulmeester E, Pereg Y, Shiloh Y, Jochemsen AG. Atm-mediated phosphorylations inhibit mdmx/mdm2 stabilization by hausp in favor of p53 activation. Cell Cycle 2005; 4:1166-70.
38. Honda R, Yasuda H. Association of p19(arf) with mdm2 inhibits ubiquitin ligase activity of mdm2 for tumor suppressor p53. Embo J 1999; 18:22-7.
39. Nazar RN. Ribosomal rna processing and ribosome biogenesis in eukaryotes. IUBMB Life 2004; 56:457-65.
40. Ruggero D, Pandolfi PP. Does the ribosome translate cancer? Nat Rev Cancer 2003; 3:179-92.
41. Amsterdam A, Sadler KC, Lai K, Farrington S, Bronson RT, Lees JA, Hopkins N. Many ribosomal protein genes are cancer genes in zebrafish. PLoS Biol 2004; 2:E139.
42. Ruggero D, Grisendi S, Piazza F, Rego E, Mari F, Rao PH, Cordon-Cardo C, Pandolfi PP. Dyskeratosis congenita and cancer in mice deficient in ribosomal rna modification. Science 2003; 299:259-62.
43. Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, Ball S, Tchernia G, Klar J, Matsson H, Tentler D, Mohandas N, Carlsson B, Dahl N. The gene encoding ribosomal protein s19 is mutated in diamond-blackfan anaemia. Nat Genet 1999; 21:169-75.
44. Choesmel V, Bacqueville D, Rouquette J, Noaillac-Depeyre J, Fribourg S, Cretien A, Leblanc T, Tchernia G, Dacosta L, Gleizes PE. Impaired ribosome biogenesis in diamond-blackfan anemia. Blood 2006.
45. Da Costa L, Tchernia G, Gascard P, Lo A, Meerpohl J, Niemeyer C, Chasis JA, Fixler J, Mohandas N. Nucleolar localization of rps19 protein in normal cells and mislocalization due to mutations in the nucleolar localization signals in 2 diamond-blackfan anemia patients: Potential insights into pathophysiology. Blood 2003; 101:5039-45.
46. Flygare J, Aspesi A, Bailey JC, Miyake K, Caffrey JM, Karlsson S, Ellis S. Human rps19, the gene mutated in diamond blackfan anemia, encodes a ribosomal protein required for the maturation of 40s ribosomal subunits. Blood 2006.
47. Ciarmatori S, Scott PH, Sutcliffe JE, McLees A, Alzuherri HM, Dannenberg JH, te Riele H, Grummt I, Voit R, White RJ. Overlapping functions of the prb family in the regulation of rrna synthesis. Mol Cell Biol 2001; 21:5806-14.
48. Hannan KM, Hannan RD, Smith SD, Jefferson LS, Lun M, Rothblum LI. Rb and p130 regulate rna polymerase i transcription: Rb disrupts the interaction between ubf and sl-1. Oncogene 2000; 19:4988-99.
49. Mora M, Darzynkiewicz Z, Baserga R. DNA synthesis and cell division in a mammalian cell mutant temperature sensitive for the processing of ribosomal rna. Exp Cell Res 1980; 125:241-9.
50. Toniolo D, Basilico C. Processing of ribosomal rna in a temperature sensitive mutant of bbk cells. Biochim Biophys Acta 1976; 425:409-18.
51. Fonagy A, Swiderski C, Dunn M, Freeman JW. Antisense-mediated specific inhibition of p120 protein expression prevents g1- to s-phase transition. Cancer Res 1992; 52:5250-6.
52. Volarevic S, Stewart MJ, Ledermann B, Zilberman F, Terracciano L, Montini E, Grompe M, Kozma SC, Thomas G. Proliferation, but not growth, blocked by conditional deletion of 40s ribosomal protein s6. Science 2000; 288:2045-7.
53. Zhao J, Yuan X, Frodin M, Grummt I. Erk-dependent phosphorylation of the transcription initiation factor tif-ia is required for rna polymerase i transcription and cell growth. Mol Cell 2003; 11:405-13.
54. Yuan X, Zhou Y, Casanova E, Chai M, Kiss E, Grone HJ, Schutz G, Grummt I. Genetic inactivation of the transcription factor tif-ia leads to nucleolar disruption, cell cycle arrest, and p53-mediated apoptosis. Mol Cell 2005; 19:77-87.
55. Strezoska Z, Pestov DG, Lau LF. Functional inactivation of the mouse nucleolar protein bop1 inhibits multiple steps in pre-rrna processing and blocks cell cycle progression. J Biol Chem 2002; 277:29617-25.
56. Pestov DG, Strezoska Z, Lau LF. Evidence of p53-dependent cross-talk between ribosome biogenesis and the cell cycle: Effects of nucleolar protein bopl on g(1)/s transition. Mol Cell Biol 2001; 21:4246-55.
57. Zhang Y, Wolf GW, Bhat K, Jin A, Allio T, Burkhart WA, Xiong Y. Ribosomal protein l11 negatively regulates oncoprotein mdm2 and mediates a p53-dependent ribosomal-stress checkpoint pathway. Mol Cell Biol 2003; 23:8902-12.
58. Dai MS, Zeng SX, Jin Y, Sun XX, David L, Lu H. Ribosomal protein 123 activates p53 by inhibiting mdm2 function in response to ribosomal perturbation but not to translation inhibition. Mol Cell Biol 2004; 24:7654-68.
59. Dai MS, Lu H. Inhibition of mdm2-mediated p53 ubiquitination and degradation by ribosomal protein 15. J Biol Chem 2004; 279:44475-82.
60. Jin A, Itahana K, O'Keefe K, Zhang Y. Inhibition of hdm2 and activation of p53 by ribosomal protein 123. Mol Cell Biol 2004; 24:7669-80.
61. Bhat KP, Itahana K, Jin A, Zhang Y. Essential role of ribosomal protein l11 in mediating growth inhibition-induced p53 activation. Embo J 2004; 23:2402-12.
62. Dai MS, Shi D, Jin Y, Sun XX, Zhang Y, Grossman SR, Lu H. Regulation of the mdm2-p53 pathway by ribosomal protein l11 involves a post-ubiquitination mechanism. J Biol Chem 2006; 281:24304-13.
63. Lohrum MA, Ludwig RL, Kubbutat MH, Hanlon M, Vousden KH. Regulation of hdm2 activity by the ribosomal protein l11. Cancer Cell 2003; 3:577-87.
64. Saxena A, Rorie CJ, Dimitrova D, Daniely Y, Borowiec JA. Nucleolin inhibits hdm2 by multiple pathways leading to p53 stabilization. Oncogene 2006; 25:7274-88.
65. Itahana K, Bhat KP, Jin A, Itahana Y, Hawke D, Kobayashi R, Zhang Y. Tumor suppressor arf degrades b23, a nucleolar protein involved in ribosome biogenesis and cell proliferation. Mol Cell 2003; 12:1151-64.
66. Korgaonkar C, Hagen J, Tompkins V, Frazier AA, Allamargot C, Quelle FW, Quelle DE. Nucleophosmin (b23) targets arf to nucleoli and inhibits its function. Mol Cell Biol 2005; 25:1258-71.
67. Chen L, Li C, Pan Y, Chen J. Regulation of p53-mdmx interaction by casein kinase 1 alpha. Mol Cell Biol 2005; 25:6509-20.
68. Gilkes DM, Chen L, Chen J. Mdmx regulation of p53 response to ribosomal stress. Embo J 2006; 25:5614-25.
69. Wang X, Arooz T, Siu WY, Chiu CH, Lau A, Yamashita K, Poon RY. Mdm2 and mdmx can interact differently with arf and members of the p53 family. FEBS Lett 2001; 490:202-8.
70. Schlott T, Reimer S, Jahns A, Ohlenbusch A, Ruschenburg I, Nagel H, Droese M. Point mutations and nucleotide insertions in the mdm2 zinc finger structure of human tumours. J Pathol 1997; 182:54-61.
71. Lindstrom MS, Jin A, Deisenroth C, Wolf GW, Zhang Y. Cancer-associated mutations in mdm2 zinc finger domain disrupt ribosomal protein interaction and attenuate mdm2-induced p53 degradation. Mol Cell Biol 2006.
72. Iapalucci-Espinoza S, Franze-Fernandez MT. Effect of protein synthesis inhibitors and low concentrations of actinomycin d on ribosomal rna synthesis. FEBS Lett 1979; 107:281-4.
73. Pritchard DM, Watson AJ, Potten CS, Jackman AL, Hickman JA. Inhibition by uridine but not thymidine of p53-dependent intestinal apoptosis initiated by 5-fluorouracil: Evidence for the involvement of rna perturbation. Proc Natl Acad Sci USA 1997; 94:1795-9.
74. Ghoshal K, Jacob ST. An alternative molecular mechanism of action of 5-fluorouracil, a potent anticancer drug. Biochem Pharmacol 1997; 53(11):1569-75.
75. Vassilev LT. Small-molecule antagonists of p53-mdm2 binding: Research tools and potential therapeutics. Cell Cycle 2004; 3:419-21.
76. Tovar C, Rosinski J, Filipovic Z, Higgins B, Kolinsky K, Hilton H, Zhao X, Vu BT, Qing W, Packman K, Myklebost O, Heimbrook DC, Vassilev LT. Small-molecule mdm2 antagonists reveal aberrant p53 signaling in cancer: Implications for therapy. Proc Natl Acad Sci USA 2006; 103:1888-93.
77. Hu B, Gilkes DM, Farooqi B, Sebti SM, Chen J. Mdmx overexpression prevents p53 activation by the mdm2 inhibitor nutlin. J Biol Chem 2006; 281:33030-5.
78. Patton JT, Mayo LD, Singhi AD, Gudkov AV, Stark GR, Jackson MW. Levels of hdmx expression dictate the sensitivity of normal and transformed cells to nutlin-3. Cancer Res 2006; 66:3169-76.
79. Wade M, Wong ET, Tang M, Stommel JM, Wahl GM. Hdmx modulates the outcome of p53 activation in human tumor cells. J Biol Chem 2006; 281:33036-44.