Regulation of p53 and NF-κB transactivation activities by DGKζ in catalytic activity-dependent and -independent manners

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, DGK zeta, is involved closely with stress responses. Morphological data showing that DGK zeta localizes predominantly to the nucleus and that it shuttles between the nucleus and the cytoplasm implicate DGK. in the regulation of transcription factors during stress responses. Tumor suppressor p53 and NF-kappa B are major stress-responsive transcription factors. They exert opposing effects on cellular pathophysiology. Herein, we summarize DGK zeta catalytic activity-dependent and -independent regulatory mechanisms of p53 and NF-kappa B transactivation activities, including p53 degradation and NF-kappa B nuclear translocation. We also discuss how each component of DGK zeta-interacting protein complex modulates the specificity and selectivity of target gene expression.

Automated summary

Diacylglycerol kinase (DGK) enzymes phosphorylate diacylglycerol to phosphatidic acid, acting as second messengers to activate cellular responses and regulate stress-responsive transcription factors like p53 and NF-kappa B. Their catalytic and non-catalytic activities modulate gene expression specificity and selectivity.