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Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):20947-51. doi: 10.1073/pnas.1015671107. Epub 2010 Nov 15.

p53-mediated apoptosis requires inositol hexakisphosphate kinase-2.

Author information

  • 1The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Inositol pyrophosphates have been implicated in numerous biological processes. Inositol hexakisphosphate kinase-2 (IP6K2), which generates the inositol pyrophosphate, diphosphoinositol pentakisphosphate (IP7), influences apoptotic cell death. The tumor suppressor p53 responds to genotoxic stress by engaging a transcriptional program leading to cell-cycle arrest or apoptosis. We demonstrate that IP6K2 is required for p53-mediated apoptosis and modulates the outcome of the p53 response. Gene disruption of IP6K2 in colorectal cancer cells selectively impairs p53-mediated apoptosis, instead favoring cell-cycle arrest. IP6K2 acts by binding directly to p53 and decreasing expression of proarrest gene targets such as the cyclin-dependent kinase inhibitor p21.

PMID:
21078964
[PubMed - indexed for MEDLINE]
PMCID:
PMC3000257
Free PMC Article

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