STRESS SIGNALING Nuclear Phospholipid Signaling

Various cellular stresses, including ultraviolet (UV) irradiation, oxidative stress, and DNA damage such as that caused by etoposide, activate cellular stress signaling and alter gene expression. Jones et al. show that these stresses, but not irradiation, promote an increase in the abundance of nuclear phosphatidylinositol-5-phosphate (PI5P) that was due to inactivation of the PI5P4-kinase ß (PIP4Kß). The activity of PIP4Kß immunoprecipitated from cells exposed to UV irradiation was decreased, and this decrease was dependent on the activity of the kinase p38 (based on analysis of cells expressing mutant forms of upstream kinases and cells exposed to pharmacological inhibitors of p38). The site of phosphorylation of PIP4Kß was mapped to Ser326. Using an antibody specific for this phosphorylated form of PIP4Kß, the authors showed that the phosphorylation of endogenous PIP4Kß was increased upon exposure of cells to UV irradiation. In vitro assays showed that PIP4Kß was a substrate for p38 and that phosphorylation by p38 decreased the kinase activity of PIP4Kß. Suppression of PIP4Kß using RNA interference resulted in increased nuclear PI5P. The increased PI5P served to recruit inhibitor of growth protein 2 (ING2) to the nucleus. ING2 is a regulator of p53, chromatin remodeling, and gene expression. Stress leads to the activation of p38 kinase, which through the inhibition of PIP4Kß increases nuclear PI5P, thereby recruiting such lipid-binding proteins as ING2 to alter gene expression.

D. R. Jones, Y. Bultsma, W.-J. Keune, J. R. Halstead, D. Elouarrat, S. Mohammed, A. J. Heck, C. S. D'Santos, N. Divecha, Nuclear PtdIns5P as a transducer of stress signaling: An in vivo role for PIP4Kbeta. Mol. Cell 23, 685-695 (2006). [PubMed]

The editors suggest the following Related Resources on Science sites:

In Science Signaling

PERSPECTIVES
Nuclear Signaling
Stress-ING Out: Phosphoinositides Mediate the Cellular Stress Response

Matthew W. Bunce, Michael L. Gonzales, and Richard A. Anderson (7 November 2006)
Sci. STKE 2006 (360), pe46. [DOI: 10.1126/stke.3602006pe46]
 |  Abstract »  |  Full Text »  |  PDF »

REVIEWS
Nuclear Lipid Signaling

Robin F. Irvine (17 September 2002)
Sci. STKE 2002 (150), re13. [DOI: 10.1126/stke.2002.150.re13]
 |  Gloss »  |  Abstract »  |  Full Text »  |  PDF »  |  Update »