Nuclear PtdIns5P as a Transducer of Stress Signaling: An In Vivo Role for PIP4Kbeta

David R. Jones, Yvette Bultsma, Willem Jan Keune, Jonathan R. Halstead, Dallila Elouarrat, Shabaz Mohammed, Albert J. Heck, Clive S S. D'Santos, Nullin Divecha*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Inhibitor of growth protein-2 (ING2) is a nuclear adaptor protein that can regulate p53 and histone acetylation in response to cellular stress and contains a PHD (plant homeodomain) finger that can interact with phosphatidylinositol-5-phosphate (PtdIns5P). However, whether or how nuclear PtdIns5P levels are regulated in response to cellular stress or whether ING2 can sense these changes has not been demonstrated. We show that UV irradiation increases nuclear PtdIns5P levels via inhibition of the activity of the β isoform of PtdIns5P 4-kinase (PIP4Kbeta), an enzyme that can phosphorylate and remove PtdIns5P. Inhibition of PIP4Kbeta activity occurs through the direct phosphorylation of PIP4Kbeta at Ser326 by the p38 stress-activated protein kinase. Finally, we show that changes in nuclear PtdIns5P are translated into changes in the association of ING2 with chromatin. Our data define a pathway connecting cellular stressors with changes in nuclear PtdIns5P levels and the regulation of PHD motif-containing proteins.

Original languageEnglish
Pages (from-to)685-695
Number of pages11
JournalMolecular Cell
Volume23
Issue number5
DOIs
Publication statusPublished - 1 Sept 2006

Keywords

  • CELLCYCLE
  • PROTEINS

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