P53-mediated apoptosis requires inositol hexakisphosphate kinase-2

Michael 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

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Inositol
Apoptosis
Cell Cycle Checkpoints
Cyclin-Dependent Kinase Inhibitor p21
Biological Phenomena
Diphosphates
DNA Damage
Colorectal Neoplasms
Cell Death
Gene Expression
Genes
inositol hexakisphosphate kinase
Neoplasms
diphosphoric acid
1-diphosphoinositol pentakisphosphate

ASJC Scopus subject areas

  • General

Cite this

P53-mediated apoptosis requires inositol hexakisphosphate kinase-2. / Koldobskiy, Michael; Chakraborty, Anutosh; Werner, J. Kent; Snowman, Adele M; Juluri, Krishna R.; Vandiver, M. Scott; Kim, Seyun; Heletz, Shira; Snyder, Solomon H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 49, 07.12.2010, p. 20947-20951.

Research output: Contribution to journalArticle

Koldobskiy, Michael ; Chakraborty, Anutosh ; Werner, J. Kent ; Snowman, Adele M ; Juluri, Krishna R. ; Vandiver, M. Scott ; Kim, Seyun ; Heletz, Shira ; Snyder, Solomon H. / P53-mediated apoptosis requires inositol hexakisphosphate kinase-2. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 49. pp. 20947-20951.
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