MDM2-Regulated Degradation of HIPK2 Prevents p53Ser46 Phosphorylation and DNA Damage-Induced Apoptosis

Molecular Cell

Volumn 25, Issue 5, 2007, Pages 739-750

  Rinaldo, Cinzia ^a   Prodosmo, Andrea ^a   Mancini, Francesca ^a,b   Iacovelli, Stefano ^a   Sacchi, Ada ^a   Moretti, Fabiola ^a,b   Soddu, Silvia ^a  

^a REGINA ELENA NATIONAL CANCER INSTITUTE   (Italy)

^b CNR   (Italy)

Author keywords

CELLCYCLE; SIGNALING

Indexed keywords

CYTOSTATIC AGENT; HOMEODOMAIN INTERACTING PROTEIN KINASE 2; PROTEIN MDM2; PROTEIN P53; SERINE;

ANIMAL CELL; APOPTOSIS; ARTICLE; CELL CYCLE ARREST; CELL FUNCTION; DNA DAMAGE; ENZYME REPRESSION; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; NONHUMAN; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING;

AMINO ACID SEQUENCE; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CARRIER PROTEINS; CATALYSIS; DNA DAMAGE; GENE EXPRESSION PROFILING; HUMANS; LYSINE; MICE; MODELS, BIOLOGICAL; MOLECULAR SEQUENCE DATA; MUTAGENS; MUTANT PROTEINS; PHOSPHORYLATION; PHOSPHOSERINE; PROTEIN BINDING; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-MDM2; TUMOR SUPPRESSOR PROTEIN P53;

EID: 33847365838     PISSN: 10972765     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.molcel.2007.02.008     Document Type: Article

References (45)

1. Appella E., and Anderson C.W. Post-translational modifications and activation of p53 by genotoxic stresses. Eur. J. Biochem. 268 (2001) 2764-2772
2. Ashcroft M., Taya Y., and Vousden K.H. Stress signals utilize multiple pathways to stabilize p53. Mol. Cell. Biol. 20 (2000) 3224-3233
3. Bartek J., and Lukas J. Mammalian G1- and S-phase checkpoints in response to DNA damage. Curr. Opin. Cell Biol. 13 (2001) 738-747
4. Bres V., Kiernan R.E., Linares L.K., Chable-Bessia C., Plechakova O., Treand C., Emiliani S., Peloponese J.M., Jeang K.T., Coux O., et al. A non-proteolytic role for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter. Nat. Cell Biol. 5 (2003) 754-761
5. Bunz F., Dutriax A., Lengauer C., Waldman T., Zhou S., Brown J.P., Sedivy J.M., Kinzler K.W., and Vogelstein B. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282 (1998) 1497-1501
6. Bulavin D.V., Saito S., Hollander M.C., Sakaguchi K., Anderson C.W., Appella E., and Fornace Jr. A.J. Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation. EMBO J. 18 (1999) 6845-6854
7. Cecchinelli B., Lavra L., Rinaldo C., Iacovelli S., Gurtner A., Gasbarri A., Ulivieri A., Del Prete F., Trovato M., Piaggio G., et al. Repression of the anti-apoptotic molecule galectin-3 by HIPK2-activated p53 is required for p53-induced apoptosis. Mol. Cell. Biol. 26 (2006) 4746-4757
8. Cecchinelli B., Porrello A., Lazzari C., Gradi A., Bossi G., D'Angelo M., Sacchi A., and Soddu S. Ser58 of mouse p53 is the homologue of human Ser46 and is phosphorylated by HIPK2 in apoptosis. Cell Death Differ. 11 (2006) 1994-1997
9. Di Stefano V., Blandino G., Sacchi A., Soddu S., and D'Orazi G. HIPK2 neutralizes MDM2 inhibition rescuing p53 transcriptional activity and apoptotic function. Oncogene 23 (2004) 5185-5192
10. Di Stefano V., Rinaldo C., Sacchi A., Soddu S., and D'Orazi G. Homeodomain-interacting protein kinase-2 activity and p53 phosphorylation are critical events for cisplatin-mediated apoptosis. Exp. Cell Res. 293 (2004) 311-320
11. D'Orazi G., Cecchinelli B., Bruno T., Manni I., Higashimoto Y., Saito S., Gostissa M., Coen S., Marchetti A., Del Sal G., et al. Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser46 and mediates apoptosis. Nat. Cell Biol. 4 (2002) 11-19
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 (2000) 8945-8951
13. Gresko E., Roscic A., Ritterhoff S., Vichalkovski A., Del Sal G., and Schmitz M.L. Autoregolatory control of the p53 response by caspase-mediated processing of HIPK2. EMBO J. 25 (2006) 1883-1894
14. Harris S.L., and Levine A.J. The p53 pathway: positive and negative feedback loops. Oncogene 24 (2005) 2899-2908
15. Haupt Y., Maya R., Kazaz A., and Oren M. Mdm2 promotes the rapid degradation of p53. Nature 387 (1997) 296-299
16. Hofmann T.G., Moller A., Sirma H., Zentgraf H., Taya Y., Droge W., Will H., and Schmitz M.L. Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2. Nat. Cell Biol. 4 (2002) 1-10
17. Honda R., Tanaka H., and Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 420 (1997) 25-27
18. Ichwan S.J., Yamada S., Sumrejkanchanakij P., Ibrahim-Auerkari E., Eto K., and Ikeda M.A. Defect in serine 46 phosphorylation of p53 contributes to acquisition of p53 resistance in oral squamous cell carcinoma cells. Oncogene 25 (2005) 1216-1224
19. Iwakuma T., and Lozano G. MDM2 an introduction. Mol. Cancer Res. 1 (2003) 993-1000
20. Kern S.E., Pietenpol J.A., Thiagalingam S., Seymour A., Kinzler K.W., and Vogelstein B. Oncogenic forms of p53 inhibit p53-regulated gene expression. Science 256 (1992) 827-830
21. Kim Y.H., Choi C.Y., Lee S.J., Conti M.A., and Kim Y. Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors. J. Biol. Chem. 273 (1998) 25875-25879
22. Kim E.-J., Park J.-S., and Um S.-J. Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo. J. Biol. Chem. 277 (2002) 32020-32028
23. Kubbutat M.H., Jones S.N., and Vousden K.H. Regulation of p53 stability by Mdm2. Nature 387 (1997) 299-303
24. Lavin M.F., and Gueven N. The complexity of p53 stabilization and activation. Cell Death Differ. 13 (2006) 941-950
25. Li X., Dumont P., Della Pietra A., Shetler C., and Murphy M.E. The codon 47 polymorphism in p53 is functionally significant. J. Biol. Chem. 280 (2005) 24245-24251
26. Marine J.-C., Francoz S., Maetens M., Wahl G., Toledo F., and Lozano G. Keeping p53 in check: essential and synergistic functions of Mdm2 and Mdm4. Cell Death Differ. 13 (2006) 927-934
27. Mayo L.D., Seo Y.R., Jackson M.W., Smith M.L., Rivera Guzman J., Korgaonkar C.K., and Donner D.B. Phosphorylation of human p53 at Ser46 determines promoter selection and whether apoptosis is attenuated or amplified. J. Biol. Chem. 280 (2005) 25953-25959
28. Moll U.M., Wolff S., Speidel D., and Deppert W. Transcription-independent pro-apoptotic functions of p53. Curr. Opin. Cell Biol. 17 (2005) 631-636
29. Moller A., Sirma H., Hofmann T.G., Rueffer S., Klimczak E., Droge W., Will H., and Schmitz M.L. PML is required for homeodomain-interacting protein kinase 2 (HIPK2)-mediated p53 phosphorylation and cell cycle arrest but is dispensable for the formation of HIPK domains. Cancer Res. 63 (2003) 4310-4314
30. 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 (1995) 203-206
31. Oda K., Arakawa H., Tanaka T., Matsuda K., Tanikawa C., Mori T., Nishimori H., Tamai K., Tokino T., Nakamura Y., and Taya Y. p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phsphorylated p53. Cell 102 (2000) 849-862
32. Ohtani S., Kagawa S., Tango Y., Umeoka T., Tokunaga N., Tsunemitsu Y., Roth J.A., Taya Y., Tanaka N., and Fujiwara T. Quantitative analysis of p53-targeted gene expression and visualization of p53 transcriptional activity following intratumoral administration of adenoviral p53 in vivo. Mol. Cancer Ther. 3 (2004) 93-100
33. Oren M. Decision making by p53: life, death and cancer. Cell Death Differ. 10 (2003) 431-442
34. Perry M.E. Mdm2 in the response to radiation. Mol. Cancer Res. 2 (2004) 9-19
35. 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 (1993) 11623-11627
36. Prives C. Signaling to p53: breaking the MDM2-p53 circuit. Cell 95 (1998) 5-8
37. Rodicker F., and Putzer B.M. p73 is effective in p53-null pancreatic cancer cells resistant to WT TP53 gene replacement. Cancer Res. 63 (2003) 2737-2741
38. Rui Y., Xu Z., Lin S., Li Q., Rui H., Luo W., Zhou H.M., Cheung P.Y., Wu Z., Ye Z., et al. Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation. EMBO J. 23 (2004) 4583-4594
39. Vassilev L.T., Vu B.T., Graves B., Carvajal D., Podlaski F., Filipovic Z., Kong N., Kammlott U., Lukacs C., Klein C., et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303 (2004) 844-848
40. Vogelstein B., Lane D., and Levine A.J. Surfing the p53 network. Nature 408 (2000) 307-310
41. Vousden K.H., and Lu X. Live or let die: the cell's response to p53. Nat. Rev. Cancer 2 (2002) 594-604
42. Wang Y., Debatin K.M., and Hug H. HIPK2 overexpression leads to stabilization of p53 protein and increased p53 transcriptional activity by decreasing Mdm2 protein levels. BMC Mol. Biol. 2 (2001) 8-16
43. Welchman R.L., Gordon C., and Mayer R.J. Ubiquitin and ubiquitin-like proteins as multifunctional signals. Nat. Rev. Mol. Cell Biol. 6 (2005) 599-609
44. Yee K.S., and Vousden K.H. Complicating the complexity of p53. Carcinogenesis 26 (2005) 1317-1322
45. Zhang Q., Yoshimatsu Y., Hildebrand J., Frisch S.M., and Goodman R.H. Homeodomain interacting protein kinase 2 promotes apoptosis by down-regulating the transcriptional co-repressor CtBP. Cell 115 (2003) 177-186