Site-specific phosphorylation of IκBα by a novel ubiquitination- dependent protein kinase activity

Z. J. Chen, L. Parent, T. Maniatis

Research output: Contribution to journalArticle

827 Scopus citations

Abstract

Signal-induced activation of the transcription factor NF-κB requires specific phosphorylation of the inhibitor IκBα and its subsequent proteolytic degradation. Phosphorylation of serine residues 32 and 36 targets IκBα to the ubiquitin (Ub)-proteasome pathway. Here we report the identification of a large, multisubunit kinase (molecular mass ~700 kDa) that phosphorylates IκBα at S32 and S36. Remarkably, the activity of this kinase requires the Ub-activating enzyme (E1), a specific Ub carrier protein (E2) of the Ubc4/Ubc5 family, and Ub. We also show that a ubiquitination event in the kinase complex is a prerequisite for specific phosphorylation of IκBα. Thus, ubiquitination serves a novel regulatory function that does not involve proteolysis.

Original languageEnglish (US)
Pages (from-to)853-862
Number of pages10
JournalCell
Volume84
Issue number6
DOIs
Publication statusPublished - 1996

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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