Phosphorylation of the Regulators, a Complex Facet of NF-?B Signaling in Cancer.

ABSTRACT: The nuclear factor kappa B (NF-?B) is a ubiquitous transcription factor central to inflammation and various malignant diseases in humans. The regulation of NF-?B can be influenced by a myriad of post-translational modifications (PTMs), including phosphorylation, one of the most popular PTM formats in NF-?B signaling. The regulation by phosphorylation modification is not limited to NF-?B subunits, but it also encompasses the diverse regulators of NF-?B signaling. The differential site-specific phosphorylation of NF-?B itself or some NF-?B regulators can result in dysregulated NF-?B signaling, often culminating in events that induce cancer progression and other hyper NF-?B related diseases, such as inflammation, cardiovascular diseases, diabetes, as well as neurodegenerative diseases, etc. In this review, we discuss the regulatory role of phosphorylation in NF-?B signaling and the mechanisms through which they aid cancer progression. Additionally, we highlight some of the known and novel NF-?B regulators that are frequently subjected to phosphorylation. Finally, we provide some future perspectives in terms of drug development to target kinases that regulate NF-?B signaling for cancer therapeutic purposes.

SUBMITTER: Motolani A 

PROVIDER: S-EPMC7823564 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature