HIPK2 regulation by MDM2 determines tumor cell response to the p53-reactivating drugs Nutlin-3 and RITA

Cancer Research

Volumn 69, Issue 15, 2009, Pages 6241-6248

  Rinaldo, Cinzia ^a   Prodosmo, Andrea ^a   Siepi, Francesca ^a   Moncada, Alice ^a   Sacchi, Ada ^a   Selivanova, Galina ^b   Soddu, Silvia ^a  

^a REGINA ELENA NATIONAL CANCER INSTITUTE   (Italy)

^b KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; FURAN DERIVATIVE; HOMEODOMAIN INTERACTING PROTEIN KINASE 2; MESSENGER RNA; NUTLIN 3; PROTEIN INHIBITOR; PROTEIN MDM2; PROTEIN P53; REACTIVATION OF P53 AND INDUCTION OF TUMOR CELL APOPTOSIS; SMALL INTERFERING RNA; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CELL PROLIFERATION; CELL VIABILITY; COLONY FORMATION; CONTROLLED STUDY; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG TARGETING; HUMAN; HUMAN CELL; MITOSIS INHIBITION; NICK END LABELING; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REAL TIME POLYMERASE CHAIN REACTION; RNA INTERFERENCE; TRANSIENT TRANSFECTION; TUMOR CELL; WESTERN BLOTTING;

APOPTOSIS; CARRIER PROTEINS; CELL LINE, TUMOR; FURANS; HCT116 CELLS; HUMANS; IMIDAZOLES; MITOSIS; PIPERAZINES; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-MDM2; RNA, MESSENGER; TUMOR SUPPRESSOR PROTEIN P53; UP-REGULATION;

EID: 68049131458     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-09-0337     Document Type: Article

References (43)

1. Soussi T, Wiman KG. Shaping genetic alterations in human cancer: the p53 mutation paradigm. Cancer Cell 2007;12:303-312 (Pubitemid 47539312)
2. Chène P. Inhibiting the p53-2 interaction: an important target for cancer therapy. Nat Rev Cancer 2003;3: 102-109 (Pubitemid 37328877)
3. Lain S, Lane D. Improving cancer therapy by nongenotoxic activation of p53. Eur J Cancer 2003;39: 1053-1060 (Pubitemid 36555861)
4. Dey A, Verma CS, Lane DP. Updates on p53: modulation of p53 degradation as a therapeutic approach. Br J Cancer 2008;98:4-8.
5. Chène P. Inhibition of the p53-2 interaction: targeting a protein-protein interface. Mol Cancer Res 2004;2: 20-28 (Pubitemid 38167104)
6. Vassilev LT. MDM2 inhibitors for cancer therapy. Trends Mol Med 2007;13:23-31.
7. Tovar C, Rosinski J, Filipovic Z, et al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci U S A 2006;103:1888-1893 (Pubitemid 43228788)
8. Issaeva N, Bozko P, Enge M, et al. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med 2004;10: 1321-1328 (Pubitemid 40022713)
9. Shmueli A, Oren M. Mdm2: p53's lifesaver? Mol Cell 2007;25:794-796
10. Rinaldo C, Prodosmo A, Mancini F, et al. MDM2- regulated degradation of HIPK2 prevents p53Ser46 phosphorylation and DNA damage-induced apoptosis. Mol Cell 2007;25:739-750 (Pubitemid 46341925)
11. Calzado MA, Renner F, Roscic A, Schmitz ML. HIPK2: a versatile switchboard regulating the transcription machinery and cell death. Cell Cycle 2007;15:139-143 (Pubitemid 46232491)
12. Rinaldo C, Prodosmo A, Siepi F, Soddu S. HIPK2: a multitalented partner for transcription factors in DNA damage response and development. Biochem Cell Biol 2007;85:411-418 (Pubitemid 47518036)
13. D'Orazi G, Cecchinelli B, Bruno T, et al. Homeodomain- interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis. Nat Cell Biol 2002;4:11-19 (Pubitemid 34071975)
14. Hofmann TG, Möller A, Sirma H, et al. Regulation of p53 activity by its interaction with homeodomaininteracting protein kinase-2. Nat Cell Biol 2002;4:1-10. (Pubitemid 34071974)
15. Oda K, Arakawa H, Tanaka T, et al. p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell 2000;102: 849-862
16. Zhang Q, Yoshimatsu Y, Hildebrand J, Frisch SM, Goodman RH. Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP. Cell 2003;115:177-186 (Pubitemid 37329581)
17. Vassilev LT, Vu BT, Graves B, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004;303:844-848
18. Xia M, Knezevic D, Tovar C, Huang B, Heimbrook DC, Vassilev LT. Elevated MDM2 boosts the apoptotic activity of p53-2 binding inhibitors by facilitating MDMX degradation. Cell Cycle 2008;7:1604-1612 (Pubitemid 351881328)
19. Cecchinelli B, Lavra L, Rinaldo C, et al. Repression of the antiapoptotic molecule galectin-3 by homeodomaininteracting protein kinase 2-activated p53 is required for p53-induced apoptosis. Mol Cell Biol 2006;26:4746-4757 (Pubitemid 43877589)
20. Brès V, Kiernan RE, Linares LK, et al. A nonproteolytic role for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter. Nat Cell Biol 2003;5: 754-761 (Pubitemid 36986784)
21. Sarek G, Kurki S, Enbäck J, et al. Reactivation of the p53 pathway as a treatment modality for KSHV-induced lymphomas. J Clin Invest 2007;117:1019-1028 (Pubitemid 46556758)
22. Enge M, Bao W, Hedström E, Jackson SP, Moumen A, Selivanova G. MDM2-dependent downregulation of p21 and hnRNP K provides a switch between apoptosis and growth arrest induced by pharmacologically activated p53. Cancer Cell 2009;15:171-183
23. Gresko E, Roscic A, Ritterhoff S, Vichalkovski A, del Sal G, Schmitz ML. Autoregulatory control of the p53 response by caspase-mediated processing of HIPK2. EMBO J 2006;25:1883-1894
24. Iwakuma T, Lozano G. MDM2, an introduction. Mol Cancer Res 2003;1:993-1000.
25. Ambrosini G, Sambol EB, Carvajal D, Vassilev LT, Singer S, Schwartz GK. Mouse double minute antagonist Nutlin-3a enhances chemotherapy-induced apoptosis in cancer cells with mutant p53 by activating E2F1. Oncogene 2007;26:3473-3481 (Pubitemid 46816754)
26. Selivanova G, Wiman KG. Reactivation of mutant p53: molecular mechanisms and therapeutic potential. Oncogene 2007;26:2243-2254 (Pubitemid 46536645)
27. Bossi G, Sacchi A. Restoration of wild-type p53 function in human cancer: relevance for tumor therapy. Head Neck 2007;29:272-284 (Pubitemid 46339325)
28. Wade M, Rodewald LW, Espinosa JM, Wahl GM. BH3 activation blocks Hdmx suppression of apoptosis and cooperates with Nutlin to induce cell death. Cell Cycle 2008;7:1973-1982 (Pubitemid 352030342)
29. LaRusch GA, Jackson MW, Dunbar JD, Warren RS, Donner DB, Mayo LD. Nutlin3 blocks vascular endothelial growth factor induction by preventing the interaction between hypoxia inducible factor 1α and Hdm2. Cancer Res 2007;67:450-454
30. Kitagawa M, Aonuma M, Lee SH, Fukutake S, McCormick F. E2F-1 transcriptional activity is a critical determinant of Mdm2 antagonist-induced apoptosis in human tumor cell lines. Oncogene 2008;27:5303-5314
31. 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;66:3169-3176
32. Hu B, Gilkes DM, Farooqi B, Sebti SM, Chen J. MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin. J Biol Chem 2006;281:33030-33035 (Pubitemid 46036685)
33. Laurie NA, Donovan SL, Shih CS, et al. Inactivation of the p53 pathway in retinoblastoma. Nature 2006;444:61-66
34. 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;281:33036-33044 (Pubitemid 46036686)
35. Mayo LD, Seo YR, Jackson MW, et al. Phosphorylation of human p53 at serine 46 determines promoter selection and whether apoptosis is attenuated or amplified. J Biol Chem 2005;280:25953-25959
36. Zacchi P, Gostissa M, Uchida T, et al. The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults. Nature 2002;419:853-857 (Pubitemid 35238573)
37. Mantovani F, Tocco F, Girardini J, et al. The prolyl isomerase Pin1 orchestrates p53 acetylation and dissociation from the apoptosis inhibitor iASPP. Nat Struct Mol Biol 2007;14:912-920 (Pubitemid 47525182)
38. Li M, Brooks CL, Wu-Baer F, Chen D, Baer R, Gu W. Mono-versus polyubiquitination: differential control of p53 fate by Mdm2. Science 2003;302:1972-1975 (Pubitemid 37523506)
39. Espinoza-Fonseca LM. Targeting MDM2 by the small molecule RITA: towards the development of new multitarget drugs against cancer. Theor Biol Med Model 2005;2:38.
40. van Amerongen R, Berns A. Targeted anticancer therapies: mouse models help uncover the mechanisms of tumor escape. Cancer Cell 2008;13:5-7. (Pubitemid 350309746)
41. Ringshausen I, O'Shea CC, Finch AJ, Swigart LB, Evan GI. Mdm2 is critically and continuously required to suppress lethal p53 activity in vivo . Cancer Cell 2006;10: 501-514 (Pubitemid 44854749)
42. Yang Y, Ludwig RL, Jensen JP, et al. Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell 2005;7: 547-559 (Pubitemid 40799248)
43. Winter M, Sombroek D, Dauth I, et al. Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR. Nat Cell Biol 2008;10: 812-824 (Pubitemid 351927710)