RRC ID 63744
Author Shoji S, Hanada K, Takahashi M, Watanabe K, Yonemochi M, Tomabechi Y, Shirouzu M.
Title The NF-κB regulator IκBβ exhibits different molecular interactivity and phosphorylation status from IκBα in an IKK2-catalysed reaction.
Journal FEBS Lett
Abstract Activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor, a central player in immune response regulation, is based on phosphorylation of inhibitor of kappaB alpha (IκBα) by the Inhibitor of kappaB kinase (IKK) that triggers IκBα degradation. Although inhibitor of kappaB beta (IκBβ) is structurally similar to IκBα, its precise characteristics remain undefined. Herein, we report that the molecular interactivity of IκBβ with the kinase-active region of IKK subunit 2 (IKK2), as well as its phosphorylation status, differs markedly from those of IκBα. A mass spectrometry analysis revealed that IκBβ phosphorylation sites are distributed in its C-terminal region, whereas IκBα phosphorylation sites are located in the N-terminal region. Furthermore, IKK2 phosphorylation sites in IκBβ are found in a region distinct from typical degradation signals, such as phosphodegron and proline/glutamic acid/serine/threonine-rich sequence (PEST) motifs. Mutation of the IκBβ phosphorylation sites enhances its resistance to homeostatic proteasomal degradation. These findings contribute a novel concept in NF-κB/IKK signalling research.
Volume 594(10)
Pages 1532-1549
Published 2020-5-1
DOI 10.1002/1873-3468.13752
PMID 32017069
MeSH Amino Acid Motifs Biocatalysis* Homeostasis Humans I-kappa B Kinase / metabolism* I-kappa B Proteins / chemistry* I-kappa B Proteins / metabolism* Models, Molecular Mutation NF-KappaB Inhibitor alpha / chemistry* NF-KappaB Inhibitor alpha / metabolism* NF-kappa B / metabolism* Phosphorylation / genetics Proteasome Endopeptidase Complex / metabolism Protein Binding Proteolysis Signal Transduction
IF 3.057
Human and Animal Cells 293T(RCB2202)