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P53-mediated apoptosis requires inositol hexakisphosphate kinase-2.

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.

SUBMITTER: Koldobskiy MA

PROVIDER: S-EPMC3000257 | biostudies-other | 2010 Dec

REPOSITORIES: biostudies-other

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p53-mediated apoptosis requires inositol hexakisphosphate kinase-2.

Koldobskiy Michael A MA Chakraborty Anutosh A Werner J Kent JK Snowman Adele M AM Juluri Krishna R KR Vandiver M Scott MS Kim Seyun S Heletz Shira S Snyder Solomon H SH

Proceedings of the National Academy of Sciences of the United States of America 20101115 49

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 disru ...[more]

PMID: 21078964

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