Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
Biochim Biophys Acta Mol Cell Res. 2021 Apr;1868(4):118953. doi: 10.1016/j.bbamcr.2021.118953. Epub 2021 Jan 13.
Diacylglycerol kinase (DGK) constitutes a family of enzymes that phosphorylate diacylglycerol to phosphatidic acid (PA). These lipids serve as second messengers, thereby activating distinct downstream cascades and different cellular responses. Therefore, DG-to-PA conversion activity induces a phase transition of signaling pathways. One member of the family, DGKζ, is involved closely with stress responses. Morphological data showing that DGKζ localizes predominantly to the nucleus and that it shuttles between the nucleus and the cytoplasm implicate DGKζ in the regulation of transcription factors during stress responses. Tumor suppressor p53 and NF-κB are major stress-responsive transcription factors. They exert opposing effects on cellular pathophysiology. Herein, we summarize DGKζ catalytic activity-dependent and -independent regulatory mechanisms of p53 and NF-κB transactivation activities, including p53 degradation and NF-κB nuclear translocation. We also discuss how each component of DGKζ-interacting protein complex modulates the specificity and selectivity of target gene expression.
二酰基甘油激酶（DGK）构成了一组能够将二酰基甘油磷酸化为磷酸脂酰肌醇（PA）的酶。这些脂质作为第二信使，从而激活不同的下游级联反应和不同的细胞反应。因此，DG 向 PA 的转化活性诱导信号通路的相变。该家族的一个成员，DGKζ，与应激反应密切相关。形态学数据表明，DGKζ主要定位于细胞核，并且在细胞核和细胞质之间穿梭，这表明 DGKζ参与了应激反应期间转录因子的调节。肿瘤抑制因子 p53 和 NF-κB 是主要的应激反应转录因子。它们对细胞病理生理学有相反的影响。在此，我们总结了 DGKζ 催化活性依赖性和非依赖性调节 p53 和 NF-κB 反式激活活性的机制，包括 p53 降解和 NF-κB 核易位。我们还讨论了 DGKζ 相互作用蛋白复合物的每个组成部分如何调节靶基因表达的特异性和选择性。
