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Updated: Apr 12, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
IκBβ enhances the generation of the low-affinity NFκB/RelA homodimer
Rachel Tsui1,2,3, Jeffrey D Kearns1,3, Candace Lynch1,3
1Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Dr M/C 0375, La Jolla, California, 92093-0375.
Abstract:
The NFκB family of dimeric transcription factors regulate inflammatory and immune responses. While the dynamic control of NFκB dimer activity via the IκB-NFκB 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-NFκB generation module. Our study reveals that IκBβ has essential functions within the Rel-NFκB generation module, specifically for the RelA:RelA homodimer, which controls a subset of NFκB target genes. Our findings revise the current dogma of the three classical, functionally related IκB proteins by distinguishing between a positive 'licensing' factor (IκBβ) that contributes to determining the available NFκB dimer repertoire in a cell's steady state, and negative feedback regulators (IκBα and -ɛ) that determine the duration and dynamics of the cellular response to an inflammatory stimulus.
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