The regulation of sequence specific NF-?B DNA binding and transcription by IKK? phosphorylation of NF-?B p50 at serine 80.

ABSTRACT: Phosphorylation of the NF-?B transcription factor is an important regulatory mechanism for the control of transcription. Here we identify serine 80 (S80) as a phosphorylation site on the p50 subunit of NF-?B, and IKK? as a p50 kinase. Transcriptomic analysis of cells expressing a p50 S80A mutant reveals a critical role for S80 in selectively regulating the TNF? inducible expression of a subset of NF-?B target genes including pro-inflammatory cytokines and chemokines. S80 phosphorylation regulates the binding of p50 to NF-?B binding (?B) sites in a sequence specific manner. Specifically, phosphorylation of S80 reduces the binding of p50 at ?B sites with an adenine at the -1 position. Our analyses demonstrate that p50 S80 phosphorylation predominantly regulates transcription through the p50:p65 heterodimer, where S80 phosphorylation acts in trans to limit the NF-?B mediated transcription of pro-inflammatory genes. The regulation of a functional class of pro-inflammatory genes by the interaction of S80 phosphorylated p50 with a specific ?B sequence describes a novel mechanism for the control of cytokine-induced transcriptional responses.

SUBMITTER: Smith EL 

PROVIDER: S-EPMC6868378 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature