| First Author | Tsui R | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7068 | PubMed ID | 25946967 |
| Mgi Jnum | J:224891 | Mgi Id | MGI:5689246 |
| Doi | 10.1038/ncomms8068 | Citation | Tsui R, et al. (2015) IkappaBbeta enhances the generation of the low-affinity NFkappaB/RelA homodimer. Nat Commun 6:7068 |
| abstractText | The NFkappaB family of dimeric transcription factors regulate inflammatory and immune responses. While the dynamic control of NFkappaB dimer activity via the IkappaB-NFkappaB 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-NFkappaB generation module. Our study reveals that IkappaBbeta has essential functions within the Rel-NFkappaB generation module, specifically for the RelA:RelA homodimer, which controls a subset of NFkappaB target genes. Our findings revise the current dogma of the three classical, functionally related IkappaB proteins by distinguishing between a positive 'licensing' factor (IkappaBbeta) that contributes to determining the available NFkappaB dimer repertoire in a cell's steady state, and negative feedback regulators (IkappaBalpha and -varepsilon) that determine the duration and dynamics of the cellular response to an inflammatory stimulus. |
