P53-mediated apoptosis requires inositol hexakisphosphate kinase-2

Michael A. Koldobskiy, Anutosh Chakraborty, J. Kent Werner, Adele M. Snowman, Krishna R. Juluri, M. Scott Vandiver, Seyun Kim, Shira Heletz, Solomon H. Snyder

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)20947-20951
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number49
DOIs
StatePublished - Dec 7 2010

ASJC Scopus subject areas

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