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

二酰甘油激酶(DGK)是一种将二酰甘油磷酸化为磷脂酸的酶，参与许多细胞的病理生理反应，如癌症和细胞凋亡。我们以前的研究表明，DGKζ定位于海马神经元的胞核，但在缺血早期迅速从胞核移位到胞浆并消失，提示其参与了细胞凋亡过程。在这项研究中，我们研究了DGKζ细胞质易位与P53之间的功能联系，P53作为各种应激途径的枢纽。我们发现，胞质DGKζ在DNA损伤后诱导P53的胞质定位，并抑制P53的诱导。在神经元中，核DGK的下调。兴奋性应激后导致细胞周期异常重入，导致细胞死亡。这些结果表明，DGKζ胞浆易位对胞浆和胞核的信号转导均有明显影响。

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.