Research ArticleRedox Signaling

Regulation of Phosphatidylinositol-5-Phosphate Signaling by Pin1 Determines Sensitivity to Oxidative Stress

Science Signaling  27 Nov 2012:
Vol. 5, Issue 252, pp. ra86
DOI: 10.1126/scisignal.2003223

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Stress-Resisting Phosphoinositide Lipids

Reactive oxygen species have been associated with aging. Mice deficient in the proline isomerase Pin1 show phenotypes associated with premature aging, yet Pin1−/− mouse embryonic fibroblasts (MEFs) are resistant to oxidative stress. Keune et al. sought to understand this resistance of the Pin1−/− MEFs and identified two isoforms of the lipid kinase PI4PK, which decrease the abundance of the phosphoinositide lipid PtdIns5P, as interacting with Pin1 in a manner that depended on phosphorylation of PIP4K. Pin1−/− MEFs had increased amounts of PtdIns5P, and reducing the abundance of this lipid compromised cell viability in response to H2O2. In vitro lipid kinase assays with PIP4K suggested that the catalytic activity of Pin1 inhibited PIP4K activity. Thus, Pin1 appears to participate in a complex pathway involving the signaling lipid PtdIns5P to control cellular sensitivity to oxidative stress.