Functional role of lipid second messenger metabolizing enzyme in cell cycle and stress response

点击翻译按钮获取中文摘要

Diacylglycerol kinase (DGK), an enzyme that phosphorylates diacylglycerol to phosphatidic acid, is involved in many pathophysiological cellular responses, such as cancer and apoptosis. Our previous studies show that DGKζ, which contains a nuclear localization signal, is localized in the nucleus of hippocampal neurons but rapidly translocates from the nucleus to the cytoplasm and disappears in the early phase of ischemia, suggesting its implication in an apoptotic process. In this study we investigated the functional link between DGKζ cytoplasmic translocation and p53 that acts as the hub of various stress pathways. We found that cytoplasmic DGKζ induces cytoplasmic localization of p53 after DNA damage and suppresses p53 induction. In neurons, down-regulation of nuclear DGK. after excitotoxic stress leads to aberrant cell cycle reentry, which results in cell death. These findings suggest that DGKζ cytoplasmic translocation exerts distinct effects on signal transduction both in the cytoplasm and the nucleus.