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A Novel Route for F-box Protein-mediated Ubiquitination Links CHIP to Glycoprotein Quality Control
Journal article   Open access   Peer reviewed

A Novel Route for F-box Protein-mediated Ubiquitination Links CHIP to Glycoprotein Quality Control

Rick F Nelson, Kevin A Glenn, Victor M Miller, Hsiang Wen and Henry L Paulson
The Journal of biological chemistry, Vol.281(29), pp.20242-20251
07/21/2006
DOI: 10.1074/jbc.M602423200
PMID: 16682404
url
https://doi.org/10.1074/jbc.M602423200View
Published (Version of record) Open Access

Abstract

In SCF (Skp1/Cullin/F-box protein) ubiquitin ligases, substrate specificity is conferred by a diverse array of F-box proteins. Only in fully assembled SCF complexes, it is believed, can substrates bound to F-box proteins become ubiquitinated. Here we show that Fbx2, a brain-enriched F-box protein implicated in the ubiquitination of glycoproteins discarded from the endoplasmic reticulum, binds the co-chaperone/ubiquitin ligase CHIP (C terminus of Hsc-70-interacting protein) through a unique N-terminal PEST domain in Fbx2. CHIP facilitates the ubiquitination and degradation of Fbx2-bound glycoproteins, including unassembled NMDA receptor subunits. These findings indicate that CHIP acts with Fbx2 in a novel ubiquitination pathway that links CHIP to glycoprotein quality control in neurons. In addition, they expand the repertoire of pathways by which F-box proteins can regulate ubiquitination and suggest a new role for PEST domains as a protein interaction motif.

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