Homeodomain interacting protein kinase 2: A target for Alzheimer's beta amyloid leading to misfolded p53 and inappropriate cell survival

PLoS ONE

Volumn 5, Issue 4, 2010, Pages

  Lanni, Cristina ^a   Nardinocchi, Lavinia ^b,c   Puca, Rosa ^b,c   Stanga, Serena ^a   Uberti, Daniela ^d   Memo, Maurizio ^d   Govoni, Stefano ^a   D'Orazi, Gabriella ^b,c   Racchi, Marco ^a  

^a UNIVERSITY OF PAVIA   (Italy)

^b REGINA ELENA NATIONAL CANCER INSTITUTE   (Italy)

^c UNIVERSITY OF CHIETI   (Italy)

^d UNIVERSITY OF BRESCIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN[1-40]; AMYLOID PRECURSOR PROTEIN; HOMEDOMAIN INTERACTING PROTEIN KINASE 2; HYPOXIA INDUCIBLE FACTOR 1ALPHA; METALLOTHIONEIN II; PROTEIN P53; PROTEIN SERINE THREONINE KINASE; UNCLASSIFIED DRUG; CARRIER PROTEIN; DNA; HIPK2 PROTEIN, HUMAN;

ADULT; AGED; ALZHEIMER DISEASE; ARTICLE; CASE REPORT; CELL STRAIN HEK293; CELL SURVIVAL; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; DNA BINDING; ENZYME ACTIVITY; ENZYME BINDING; FEMALE; FIBROBLAST; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; MALE; PROTEIN CONFORMATION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN TARGETING; WESTERN BLOTTING; CELL CULTURE; CHEMISTRY; METABOLISM; PATHOLOGY; PHYSIOLOGY; PROMOTER REGION; PROTEIN BINDING;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; CARRIER PROTEINS; CELL SURVIVAL; CELLS, CULTURED; DNA; HUMANS; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; PROTEIN FOLDING; PROTEIN-SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEIN P53;

EID: 77955469129     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0010171     Document Type: Article

References (35)

1. Vousden KH, Prives C (2005) P53 and prognosis: new insights and further complexity. Cell 120: 7-10.
2. Brooks CL, Gu W (2003) Ubiquitination, phosphorylation and acetylation: the molecular basis for p53 regulation. Curr Opin Cell Biol 15: 164-171.
3. Hainaut P, Milner J (1993) Redox modulation of p53 conformation and sequence-specific DNA binding in vitro. Cancer Res 53: 4469-4473.
4. Joerger AC, Fersht AR (2007) Structure-function-rescue: the diverse nature of common p53 cancer mutants. Oncogene 26: 2226-2242.
5. Uberti D, Cenini G, Olivari L, Ferrari-Toninelli G, Porrello E, et al. (2007) Over-expression of amyloid precursor protein in HEK cells alters p53 conformational state and protects against doxorubicin. J Neurochem 103: 322-333.
6. Lanni C, Racchi M, Mazzini G, Ranzenigo A, Polotti R, et al. (2008) Conformationally altered p53: a novel Alzheimer's disease marker? Mol Psychiatry 13: 641-647.
7. Uberti D, Lanni C, Carsana T, Francisconi S, Missale C, et al. (2006) Identification of a mutant-like conformation of p53 in fibroblasts from sporadic Alzheimer's disease patients. Neurobiol Aging 27: 1193-1201.
8. Lanni C, Uberti D, Racchi M, Govoni S, Memo M (2007) Unfolded p53: a potential biomarker for Alzheimer's disease. J Alzheimers Dis 12: 93-99.
9. Rinaldo C, Prodosmo A, Siepi F, Soddu S (2007) HIPK2: a multitalented partner for transcription factors in DNA damage response and development. Biochem Cell Biol 85: 411-418.
10. 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.
11. 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.
12. Hofmann TG, Möller A, Sirma H, Zentgraf H, Taya Y, et al. (2002) Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2. Nat Cell Biol 4: 1-10.
13. 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.
14. Verdile G, Fuller S, Atwood CS, Laws SM, Gandy SE, et al. (2004) The role of beta amyloid in Alzheimer's disease: still a cause of everything or the only one who got caught? Pharmacol Res 50: 397-409.
15. Nardinocchi L, Puca R, Guidolin D, Belloni AS, Bossi G, et al. (2009) Transcriptional regulation of hypoxia-inducible factor 1alpha by HIPK2 suggests a novel mechanism to restrain tumor growth. Biochim Biophys Acta 1793: 368-377.
16. Méplan C, Richard MJ, Hainaut P (2000) Redox signalling and transition metals in the control of the p53 pathway. Biochem Pharmacol 59: 25-33.
17. 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.
18. 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.
19. Wang S, Konorev EA, Kotamraju S, Joseph J, Kalivendi S, et al. (2004) Doxorubicin induces apoptosis in normal and tumor cells via distinctly different mechanisms. Intermediacy of H(2)O(2)- and p53-dependent pathways. J Biol Chem 279: 25535-25543.
20. Nardinocchi L, Puca R, Sacchi A, Rechavi G, Givol D, et al. (2009) Targeting hypoxia in cancer cells by restoring homeodomain interacting protein-kinase 2 and p53 activity and suppressing HIF-1alpha. PLoS One 4: e6819.
21. Uberti D, Carsana T, Bernardi E, Rodella L, Grigolato P, et al. (2002) Selective impairment of p53-mediated cell death in fibroblasts from sporadic Alzheimer's disease patients. J Cell Sci 115: 3131-3138.
22. 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.
23. Nardinocchi L, Puca R, Givol D, D'Orazi G (2010) HIPK2: A therapeutical target to be (re)activated for tumor suppression. Role in p53 activation and HIF- 1a inhibition. Cell Cycle 9(7): [Epub ahead of print].
24. Calzado MA, De La Vega L, Munoz E, Schmitz ML (2009) From top to bottom. The two faces of HIPK2 for regulation of the hypoxic response. Cell Cycle 8: 1659-1664.
25. Gasparini L, Racchi M, Binetti G, Trabucchi M, Solerte SB, et al. (1998) Peripheral markers in testing pathophysiological hypotheses and diagnosing Alzheimer's disease. FASEB J 12: 17-34.
26. Bergamaschi S, Binetti G, Govoni S, Wetsel WC, Battaini F, et al. (1995) Defective phorbol ester-stimulated secretion of beta-amyloid precursor protein from Alzheimer's disease fibroblasts. Neurosci Lett 201: 1-5.
27. Doxakis E, Huang EJ, Davies AM (2004) Homeodomain-interacting protein kinase-2 regulates apoptosis in developing sensory and sympathetic neurons. Curr Biol 14: 1761-1765.
28. Wiggings AK, Wei G, Doxakis E, Wang C, Tang AA, et al. (2004) Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival. J Cell Biol 167: 257-267.
29. Zhang J, Pho V, Bonasera SJ, Holzmann J, Tang AT, et al. (2007) Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons. Nature Neurosci 10: 77-86.
30. Li H, Costantini C, Scrable H, Weindruch R, Puglielli L (2009) Egr-1 and Hipk2 are required for the TrakA to p75NTR switch that occurs downstream of IGF1- R. Neurobiol Aging 30: 2010-2020.
31. Sensi SL, Paoletti P, Bush AI, Sekler I (2009) Zinc in the physiology and pathology of the CNS. Nat Rev Neurosci 10: 780-791.
32. Ryu J, Girigoswami K, Ha C, Ku SH, Park CB (2008) Influence of multiple metal ions on beta-amyloid aggregation and dissociation on a solid surface. Biochemistry 47: 5328-5335.
33. Govoni S, Bergamaschi S, Racchi M, Battaini F, Binetti G, et al. (1993) Cytosol protein kinase c downregulation in fibroblasts from Alzheimer's disease patients. Neurology 43: 2581-2586.
34. 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.
35. Lanni C, Mazzucchelli M, Porrello E, Govoni S, Racchi M (2004) Differential involvement of protein kinase C alpha and epsilon in the regulated secretion of soluble amyloid precursor protein. Eur J Biochem 271: 3068-3075.