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The NF‐κB regulator IκBβ exhibits different molecular interactivity and phosphorylation status from IκBα in an IKK2‐catalysed reaction
Author(s) -
Shoji Shisako,
Hanada Kazuharu,
Takahashi Masataka,
Watanabe Kazuhide,
Yonemochi Mayumi,
Tomabechi Yuri,
Shirouzu Mikako
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13752
Subject(s) - phosphorylation , iκb kinase , iκbα , transcription factor , phosphorylation cascade , serine , kinase , nf κb , nfkb1 , microbiology and biotechnology , chemistry , biology , biochemistry , protein kinase a , signal transduction , protein phosphorylation , gene
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.