Inositol polyphosphate multikinase is a coactivator of p53-mediated transcription and cell death

Risheng Xu, Nilkantha Sen, Bindu D. Paul, Adele M. Snowman, Feng Rao, M. Scott Vandiver, Jing Xu, Solomon H. Snyder

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
JournalScience Signaling
Volume6
Issue number269
DOIs
StatePublished - Apr 2 2013

Fingerprint

Cell death
Transcription
Cell Death
Genes
Cells
Tumor Suppressor Protein p53
Acetylation
Inositol Phosphates
p53 Genes
RNA Interference
Cell Cycle Checkpoints
Tumors
Cell Survival
Transcription Factors
Phosphotransferases
Chemical activation
RNA
Apoptosis
Lipids
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Xu, R., Sen, N., Paul, B. D., Snowman, A. M., Rao, F., Vandiver, M. S., ... Snyder, S. H. (2013). Inositol polyphosphate multikinase is a coactivator of p53-mediated transcription and cell death. Science Signaling, 6(269). https://doi.org/10.1126/scisignal.2003405

Inositol polyphosphate multikinase is a coactivator of p53-mediated transcription and cell death. / Xu, Risheng; Sen, Nilkantha; Paul, Bindu D.; Snowman, Adele M.; Rao, Feng; Vandiver, M. Scott; Xu, Jing; Snyder, Solomon H.

In: Science Signaling, Vol. 6, No. 269, 02.04.2013.

Research output: Contribution to journalArticle

Xu, R, Sen, N, Paul, BD, Snowman, AM, Rao, F, Vandiver, MS, Xu, J & Snyder, SH 2013, 'Inositol polyphosphate multikinase is a coactivator of p53-mediated transcription and cell death', Science Signaling, vol. 6, no. 269. https://doi.org/10.1126/scisignal.2003405
Xu, Risheng ; Sen, Nilkantha ; Paul, Bindu D. ; Snowman, Adele M. ; Rao, Feng ; Vandiver, M. Scott ; Xu, Jing ; Snyder, Solomon H. / Inositol polyphosphate multikinase is a coactivator of p53-mediated transcription and cell death. In: Science Signaling. 2013 ; Vol. 6, No. 269.
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