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

https://doi.org/10.1016/j.bbamcr.2021.118953Get rights and content
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Highlights

  • DGKζ regulation of p53 protein levels is a kinase-independent or scaffolding function.

  • DGKζ depletion downregulates p53 transactivation activity.

  • Kinase-independent or scaffolding function of DGKζ in the control of IκB protein levels

  • DGKζ depletion upregulates NF-κB transactivation activity.

  • DGKζ regulates p53 and NF-κB transactivation activities in catalytic activity-dependent manner.

Abstract

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.

Keywords

Catalytic activity
CBP
DGK
NF-κB
p53
Transcription

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