Open Accessp53-mediated apoptosis requires inositol hexakisphosphate kinase-2
Author(s) -
Michael A. Koldobskiy,
Anutosh Chakraborty,
J. Kent Werner,
Adele M. Snowman,
Krishna R. Juluri,
M. Scott Vandiver,
Se-Yun Kim,
Shira Heletz,
Solomon H. Snyder
Publication year - 2010
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1015671107
Subject(s) - inositol , apoptosis , kinase , microbiology and biotechnology , cell cycle checkpoint , programmed cell death , biology , tumor suppressor gene , cell cycle , cyclin dependent kinase 4 , cyclin dependent kinase 2 , chemistry , cancer research , protein kinase a , gene , biochemistry , carcinogenesis , receptor
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.