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  • Title: p53-mediated apoptosis requires inositol hexakisphosphate kinase-2.
    Author: Koldobskiy MA, Chakraborty A, Werner JK, Snowman AM, Juluri KR, Vandiver MS, Kim S, Heletz S, Snyder SH.
    Journal: Proc Natl Acad Sci U S A; 2010 Dec 07; 107(49):20947-51. PubMed ID: 21078964.
    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.
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