I?B? enhances the generation of the low-affinity NF?B/RelA homodimer.

ABSTRACT: The NF?B family of dimeric transcription factors regulate inflammatory and immune responses. While the dynamic control of NF?B dimer activity via the I?B-NF?B signalling module is well understood, there is little information on how specific dimer repertoires are generated from Rel family polypeptides. Here we report the iterative construction-guided by in vitro and in vivo experimentation-of a mathematical model of the Rel-NF?B generation module. Our study reveals that I?B? has essential functions within the Rel-NF?B generation module, specifically for the RelA:RelA homodimer, which controls a subset of NF?B target genes. Our findings revise the current dogma of the three classical, functionally related I?B proteins by distinguishing between a positive 'licensing' factor (I?B?) that contributes to determining the available NF?B dimer repertoire in a cell's steady state, and negative feedback regulators (I?B? and -?) that determine the duration and dynamics of the cellular response to an inflammatory stimulus.

SUBMITTER: Tsui R 

PROVIDER: S-EPMC4425231 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature