AffiliationInositide Laboratory CRUK, The Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, United Kingdom
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AbstractOxidative signaling is important in cellular health, involved in aging and contributes to the development of several diseases such as cancer, neurodegeneration and diabetes. Correct management of reactive oxygen species (ROS) prevents oxidative stress within cells and is imperative for cellular wellbeing. A key pathway that is regulated by oxidative stress is the activation of proline-directed stress kinases (p38, JNK). Phosphorylation induced by these kinases is often translated into cellular outcome through the recruitment of the prolyl-isomerase Pin1. Pin1 binds to phosphorylated substrates using its WW-domain and can induce conformational changes in the target protein through its prolyl-isomerase activity. We show that exposure of cells to UV irradiation or hydrogen peroxide (H2O2), induces the synthesis of the phosphoinositide second messenger PtdIns5P in part by inducing the interaction between phosphatidylinositol-5-phosphate 4-kinase (PIP4K) enzymes that remove PtdIns5P, with Pin1. In response to H2O2 exposure, Murine Embryonic Fibroblasts (MEFs) derived from Pin1(-/-) mice showed increased cell viability and an increased abundance of PtdIns5P compared to wild-type MEFs. Decreasing the levels of PtdIns5P in Pin1(-/-) MEFs decreased both their viability in response to H2O2 exposure and the expression of genes required for cellular ROS management. The decrease in the expression of these genes manifested itself in the increased accumulation of cellular ROS. These data strongly argue that PtdIns5P acts as a stress-induced second messenger that can calibrate how cells manage ROS.
CitationPtdIns5P and Pin1 in oxidative stress signaling. 2013, 53 (2):179-89 Adv Biol Regul
JournalAdvances in Biological Regulation
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