Inositol Polyphosphate Multikinase Is a Coactivator of p53-Mediated Transcription and Cell Death

This article has a correction Sci. Signal. 6(273):er1

Sci. Signal., 2 April 2013
Vol. 6, Issue 269, p. ra22
DOI: 10.1126/scisignal.2003405

Inositol Polyphosphate Multikinase Is a Coactivator of p53-Mediated Transcription and Cell Death

  1. Risheng Xu1,2,*,
  2. Nilkantha Sen3,*,
  3. Bindu D. Paul3,
  4. Adele M. Snowman3,
  5. Feng Rao3,
  6. M. Scott Vandiver1,2,
  7. Jing Xu3, and
  8. Solomon H. Snyder1,3,4,
  1. 1Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  2. 2Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  3. 3The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  4. 4Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  1. Corresponding author. E-mail: ssnyder{at}jhmi.edu
  • * These authors contributed equally to this work.

Abstract

The tumor suppressor protein p53 is a critical stress response transcription factor that induces the expression of genes leading to cell cycle arrest, apoptosis, and tumor suppression. We found that mammalian inositol polyphosphate multikinase (IPMK) stimulated p53-mediated transcription by binding to p53 and enhancing its acetylation by the acetyltransferase p300 independently of its inositol phosphate and lipid kinase activities. Genetic or RNA interference (RNAi)–mediated knockdown of IPMK resulted in decreased activation of p53, decreased recruitment of p53 and p300 to target gene promoters, abrogated transcription of p53 target genes, and enhanced cell viability. Additionally, blocking the IPMK-p53 interaction decreased the extent of p53-mediated transcription. These results suggest that IPMK acts as a transcriptional coactivator for p53 and that it is an integral part of the p53 transcriptional complex facilitating cell death.

Citation:

R. Xu, N. Sen, B. D. Paul, A. M. Snowman, F. Rao, M. S. Vandiver, J. Xu, and S. H. Snyder, Inositol Polyphosphate Multikinase Is a Coactivator of p53-Mediated Transcription and Cell Death. Sci. Signal. 6, ra22 (2013).

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Proc. Natl. Acad. Sci. USA 110, 19938-19943 (3 December 2013)

Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction
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