Research ArticleBiochemistry

The NF-κB subunit RelB controls p100 processing by competing with the kinases NIK and IKK1 for binding to p100

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Science Signaling  27 Sep 2016:
Vol. 9, Issue 447, pp. ra96
DOI: 10.1126/scisignal.aad9413

Intermolecular competition for activation or inhibition

Noncanonical nuclear factor κB (NF-κB) signaling requires cleavage of the RelB-bound p100 precursor to generate the transcriptionally active p52:RelB heterodimer in a process dependent on the kinases NIK and IKK1. However, p100:RelB dimers also form kappaBsomes, multiprotein complexes that sequester NF-κB subunits to inhibit gene expression. Fusco et al. found that the function of p100 was determined by how RelB was bound to a transitional complex consisting of p100, NIK, and IKK1. If the binding of RelB to p100 displaced NIK and IKK1 from p100, p100 was not phosphorylated or cleaved, and instead, kappaBsomes formed. On the other hand, failure of RelB to displace the kinase complex before p100 phosphorylation resulted in the formation of the active p52:RelB dimer.

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