PMID: 8601309Mar 22, 1996Paper

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

Cell
Z J ChenT Maniatis

Abstract

Signal-induced activation of the transcription factor NF-kappaB requires specific phosphorylation of the inhibitor IkappaBalpha and its subsequent proteolytic degradation. Phosphorylation of serine residues 32 and 36 targets IkappaBalpha to the ubiquitin (Ub)-proteasome pathway. Here we report the identification of a large, multisubunit kinase (molecular mass approximately 700 kDa) that phosphorylates IkappaBalpha 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 IkappaBalpha. Thus, ubiquitination serves a novel regulatory function that does not involve proteolysis.

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