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

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 le...

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Bibliographic Details
Published in:Molecular cell 2006-09, Vol.23 (5), p.685-695
Main Authors: Jones, David R., Bultsma, Yvette, Keune, Willem-Jan, Halstead, Jonathan R., Elouarrat, Dallila, Mohammed, Shabaz, Heck, Albert J., D'Santos, Clive S., Divecha, Nullin
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 4-Kinase - chemistry
1-Phosphatidylinositol 4-Kinase - metabolism
Amino Acid Sequence
Animals
Cell Nucleus - metabolism
CELLCYCLE
Cells, Cultured
Homeodomain Proteins - metabolism
Humans
Mice
Models, Biological
Molecular Sequence Data
Oxidative Stress - radiation effects
p38 Mitogen-Activated Protein Kinases - metabolism
Phosphatidylinositol Phosphates - metabolism
Phosphorylation - radiation effects
Phosphoserine - metabolism
PROTEINS
Signal Transduction
Subcellular Fractions
Tumor Suppressor Proteins - metabolism
Ultraviolet Rays
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Summary: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.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2006.07.014