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

doi:10.1016/j.molcel.2006.07.014

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 journal › Article › Academic › peer-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 language	English
Pages (from-to)	685-695
Number of pages	11
Journal	Molecular Cell
Volume	23
Issue number	5
DOIs	https://doi.org/10.1016/j.molcel.2006.07.014
Publication status	Published - 1 Sept 2006

Bibliographical note

Funding Information:
We thank Dr. Or Gozani and Prof. Junying Yuan for the rat polyclonal anti-ING2 antibody. We also thank previous and current members of the Divecha laboratory and Maria Carla Motta. This work was partially supported by an EU-Marie Curie Individual fellowship (HPMF-CT-2002-01218) to D.R.J. and by grants from The Netherlands Cancer Institute and the Koningin Wilhemina Fonds Nederlandse Kanker Bestrijding awarded to N.D.

Funding

We thank Dr. Or Gozani and Prof. Junying Yuan for the rat polyclonal anti-ING2 antibody. We also thank previous and current members of the Divecha laboratory and Maria Carla Motta. This work was partially supported by an EU-Marie Curie Individual fellowship (HPMF-CT-2002-01218) to D.R.J. and by grants from The Netherlands Cancer Institute and the Koningin Wilhemina Fonds Nederlandse Kanker Bestrijding awarded to N.D.

Keywords

CELLCYCLE
PROTEINS

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10.1016/j.molcel.2006.07.014

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title = "Nuclear PtdIns5P as a Transducer of Stress Signaling: An In Vivo Role for PIP4Kbeta",

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.",

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author = "Jones, {David R.} and Yvette Bultsma and Keune, {Willem Jan} and Halstead, {Jonathan R.} and Dallila Elouarrat and Shabaz Mohammed and Heck, {Albert J.} and D'Santos, {Clive S S.} and Nullin Divecha",

note = "Funding Information: We thank Dr. Or Gozani and Prof. Junying Yuan for the rat polyclonal anti-ING2 antibody. We also thank previous and current members of the Divecha laboratory and Maria Carla Motta. This work was partially supported by an EU-Marie Curie Individual fellowship (HPMF-CT-2002-01218) to D.R.J. and by grants from The Netherlands Cancer Institute and the Koningin Wilhemina Fonds Nederlandse Kanker Bestrijding awarded to N.D. ",

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AU - Halstead, Jonathan R.

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AU - Mohammed, Shabaz

AU - Heck, Albert J.

AU - D'Santos, Clive S S.

AU - Divecha, Nullin

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N2 - 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.

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

Abstract

Bibliographical note

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Keywords

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