Targeting hypoxia in cancer cells by restoring homeodomain interacting protein-kinase 2 and p53 activity and suppressing HIF-1α

PLoS ONE

Volumn 4, Issue 8, 2009, Pages

  Nardinocchi, Lavinia ^a   Puca, Rosa ^a   Sacchi, Ada ^a   Rechavi, Gideon ^b   Givol, David ^c   D'Orazi, Gabriella ^a,d  

^a REGINA ELENA NATIONAL CANCER INSTITUTE   (Italy)

^b TEL AVIV UNIVERSITY   (Israel)

^c WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^d UNIVERSITY OF CHIETI   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

COBALT; DOXORUBICIN; HOMEODOMAIN INTERACTING PROTEIN KINASE 2; HYPOXIA INDUCIBLE FACTOR 1ALPHA; MULTIDRUG RESISTANCE PROTEIN 1; OXYGEN; PROTEIN BCL 2; PROTEIN MDM2; PROTEIN P53; RNA; SMALL INTERFERING RNA; VASCULOTROPIN; ZINC CHLORIDE; ANTINEOPLASTIC AGENT; CARRIER PROTEIN; HIF1A PROTEIN, HUMAN; HIPK2 PROTEIN, HUMAN; MDM2 PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE; ZINC;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL; CANCER CELL CULTURE; CANCER INHIBITION; CANCER RESISTANCE; CELL HYPOXIA; CHROMATIN IMMUNOPRECIPITATION; COLON CARCINOMA; CONTROLLED STUDY; DOWN REGULATION; DRUG MECHANISM; GENE REPRESSION; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; LUNG CANCER; MOUSE; NONHUMAN; PLASMID; PROMOTER REGION; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STABILITY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA EXTRACTION; SOLID TUMOR; UPREGULATION; WESTERN BLOTTING; DRUG EFFECT; GENETIC TRANSCRIPTION; GENETICS; METABOLISM;

ANTINEOPLASTIC AGENTS; CARRIER PROTEINS; CELL HYPOXIA; COBALT; DOXORUBICIN; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; PROMOTER REGIONS, GENETIC; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-MDM2; TRANSCRIPTION, GENETIC; TUMOR SUPPRESSOR PROTEIN P53; ZINC;

EID: 69949108875     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0006819     Document Type: Article

References (49)

1. Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nature Rev Cancer 3: 721-732.
2. Achison M, Hupp TR (2003) Hypoxia attenuates the p53 response to cellular damage. Oncogene 22: 3431-3440.
3. Vousden HK, Lane DP (2007) P53 in health and disease. Nature Rev Mol Cell Biol 8: 275-283.
4. Sakaguchi K, Herrera JE, Saito S, Miki T, Bustin M, et al. (1998) DNA damage activates p53 through a phosphorylation-acetylation cascade. Genes Dev 12: 2831-2841.
5. Hollstein M, Hergenhahn M, Yang Q, Bartsch H, Wang ZQ, et al. (1999) New approaches to understanding p53 gene tumor mutation spectra. Mutat Res 432: 199-209.
6. Vousden KH, Prives C (2005) P53 and prognosis: new insights and further complexity. Cell 120: 7-10.
7. D'Orazi G, Cecchinelli B, Bruno T, Manni I, Higashimoto Y, et al. (2002) Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis. Nat Cell Biol 4: 11-19.
8. Di Stefano V, Rinaldo C, Sacchi A, Soddu S, D'Orazi G (2004) Homeodomain-interacting protein kinase-2 activity and p53 phosphorylation are critical events for cisplatin-mediated apoptosis. Exp Cell Res 293: 311-320.
9. Pistritto G, Puca R, Nardinocchi L, Sacchi A, D'Orazi G (2007) HIPK2-induced p53Ser46 phosphorylation activates the KILLER/DR5-mediated caspase-8 extrinsic apoptotic pathway. Cell Death Diff 14: 1837-1839.
10. Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, et al. (2000) P53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell 102: 849-862.
11. Mayo LD, Seo Y, Jackson MW, Smith ML, Rivera Guzman J, et al. (2005) Phosphorylation of human p53 at serine 46 determines promoter selection and whether apoptosis is attenuated or amplified. J Biol Chem 280: 25953-25959.
12. Momand J, Zambetti GP, Olson DC, Gorge D, Levine AJ (1992) The Mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69: 1237-1245.
13. Haupt Y, Maya R, Kazaz A, Oren M (1997) MDM2 promotes the rapid degradation of p53. Nature 387: 296-299.
14. Kubbutat MH, Jones SN, Vousden KH (1997) Regulation of p53 stability by MDM2. Nature 387: 299-303.
15. Di Stefano V, Blandino G, Soddu S Sacchi A, D'Orazi G (2004) HIPK2 neutralizes MDM2 inhibition rescuing p53 transcriptional activity and apoptotic function. Oncogene 23: 5185-5192.
16. Choi CY, Kim YH, Kwon HJ, Kim Y (1999) The homeodomain protein NK-3 recruits Groucho and a histone deacetylase complex to repress transcription. J Biol Chem 274: 33194-33197.
17. Nardinocchi L, Puca R, Guidolin D, Belloni AS, Bossi G, et al. (2009) Transcriptional regulation of hypoxia-inducible factor 1a by HIPK2 suggests a novelmechanism to restrain tumor growth. Biochim Biophys Acta 1793: 368-377.
18. Nardinocchi L, Puca R, Sacchi A, D'Orazi G (2009) Inhibition of HIF-1alpha activity by homeodomain-interacting protien kinase-2 correlates with sensitization of chemoresistant cells to undergo apoptosis. Mol Cancer 8: 1.
19. Pierantoni GM, Bulfone A, Pentimalli F, Fedele M, Iuliano R, et al. (2002) The homeodomain-interacting protein kinase 2 gene is expressed late in embryogenesis and preferentially in retina, muscle, and neural tissue. Biochem Biophys Res Commun 290: 942-947.
20. D'Orazi G, Sciulli MG, Di Stefano V, Riccioni S, Frattini M, et al. (2006) Homeodomain-interacting protein kinase-2 restrains cytosolic phospholipase A2-dependent prostaglandin E2 generation in human colorectal cancer cells. Clin Cancer Res 12: 735-741.
21. Li X-L, Arai Y, Harada H, Shima Y, Yoshida H, et al. (2007) Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic sindrome impair AML1- and p53-mediated transcription. Oncogene 26: 7231-7239.
22. Pierantoni GM, Rinaldo C, Mottolese M, Di Benedetto A, Esposito F, et al. (2007) High-mobility group A1 inhibits p53 by cytoplasmic relocalization of its proapoptotic activator HIPK2. J Clin Invest 117: 693-702.
23. Rinaldo C, Prodosmo A, Mancini F, Iacovelli S, Sacchi A, et al. (2007) MDM2-regulated degradation of HIPK2 prevents p53Ser46 phosphorylation and DNA damage-induced apoptosis. Mol Cell 25: 739-750.
24. Calzado MA, de la Vega L, Moller A, Bowtell DD, Schmitz ML (2009) An inducible autoregulatory loop between HIPK2 and Siah2 at the apex of the hypoxic response. Nature Cell Biol 11: 85-91.
25. Puca R, Nardinocchi L, Gal H, Rechavi G, Amariglio N, et al. (2008) Reversible dysfunction of wild-type p53 following homeodomain-interacting protein kinase-2 knockdown. Cancer Res 68: 3707-3714.
26. Puca R, Nardinocchi L, Bossi G, Sacchi A, Rechavi G, et al. (2009) Restoring wtp53 activity in HIPK2 depleted MCF7 cells by modulating metallothionein and zinc. Exp Cell Res 315: 67-75.
27. Loges S, Mazzone M, Hohensinner P, Carmeliet P (2009) Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited. Cancer Cell 15: 167-70.
28. Joenger AC, Fersht AR (2007) Structure-function-rescue: the diverse nature of common p53 cancer mutants. Oncogene 26: 2226-2242.
29. Beyersmann D, Haase H (2001) Functions of zinc in signalling, proliferation and differentiation of mammalian cells. Biometals 14: 331-341.
30. Ho E (2004) Zinc deficiency, DNA damage and cancer risk. J Nutr Biochem 15: 572-578.
31. Shah MR, Kriedt CI, Lents NH, Hoyer MK, Jamaluddin N, et al. (2009) Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer. JECCR 28: 84.
32. Wang GL, Semenza GL (1993) General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci USA 90: 4304-4308.
33. Gresko E, Roscic A, Vichalkovski S, del Sal G, Schmitz ML (2006) Autoregulatory control of the p53 response by caspases-mediated processing of HIPK2. EMBO J 25: 1883-1894.
34. Hofmann TG, Moller A, Sirma H, Zentgraf H, Taya Y, et al. (2002) Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2. Nature Cell Biol 4: 1-10.
35. Puca R, Nardinocchi L, Pistritto G, D'Orazi G (2008) Overexpression of HIPK2 circumvents the blockade of apoptosis in chemoresistant ovarian cancer cells. Gynecol Oncol 109: 403-410.
36. Lai A, Cairns MJ, Tran N, Zhang H-P, Cullen L, et al. (2009) RNA modulators of complex phenotypes in mammalian cells. PLos ONE 4: e4758.
37. Wesierska-Gadek J, Schmitz ML, Ranftler C (2007) Roscovitine-activated HIP2 kinase induces phosphorylation of wtp53 at Ser-46 in human MCF-7 breast cancer cells. J \Cell Biochem 100: 865-874.
38. Dauth I, Kruger J, Hofmann TG (2007) Homeodomain-Interacting Protein kinase 2 is the ionizing radiation-activated p53 serine 46 kinase and is regulated by ATM. Cancer Res 67: 2274-2279.
39. Iwakuma T, Lozano G (2003) MDM2 an introduction. Mol Cancer Res 1: 993-1000.
40. Calzado MA, Renner F, Roscic A, Schmitz ML (2007) HIPK2: a versatile switchboard regulating the transcription machinery and cell death. Cell Cycle 6: 139-143.
41. Verger A, Perdomo J, Crossley M (2003) Modification with SUMO: A role in transcriptional regulation. EMBO Reports 4: 137-142.
42. Gresko E, Moller A, Roscic A, Schmitz ML (2005) Covalent modification of human homeodomain-interacting protein kinase-2 by SUMO-1 at lysine 25 affects its stability. Biochem Biophys Res Commun 329: 1293-1299.
43. Roscic A, Moller A, Calzado MA, Renner F, Wimmer VC, et al. (2006) Phosphorylation-dependent control of Pc2 SUMO E3 ligase activity by its substrate protein HIPK2. Mol Cell 24: 77-89.
44. Eby GA (2005) Treatment of acute lymphocytic leukemia using zinc adjuvant with chemotherapy and radiation - a case history and hypothesis. Medical Hypothesis 64: 1124-1126.
45. Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, et al. (2009) Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15: 220-231.
46. Ebos JML, Lee CR, Cruz-Munoz W, Bjarnason GA, Christenses JG, et al. (2009) Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15: 232-239.
47. Li X, Lu Y, Liang K, Pan T, Mendelshon J, et al. (2008) Requirement of hypoxia-inducible factor 1 alpha downregulation in mediating the antitumor activity of the anti-epidermal growth factor receptor monoclonal antibody cetuximab. Mol Cancer Ther 7: 1207-1217.
48. Di Stefano V, Soddu S, Sacchi A, D'Orazi G (2005) HIPK2 contributes to PCAF-mediated p53 acetylation and selective transactivation of p21Waf1 after non-apoptotic DNA damage. Oncogene 24: 5431-5442.
49. Chen C, Okayama H (1987) High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 7: 2745-2752.