A novel route for F-box protein-mediated ubiquitination links CHIP to glycoprotein quality control

Rick Nelson, Kevin A. Glenn, Victor M. Miller, Hsiang Wen, Henry L. Paulson

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)20242-20251
Number of pages10
JournalJournal of Biological Chemistry
Volume281
Issue number29
DOIs
StatePublished - Jul 21 2006
Externally publishedYes

Fingerprint

F-Box Proteins
Ubiquitination
Quality Control
Quality control
Glycoproteins
SKP Cullin F-Box Protein Ligases
Ligases
Ubiquitin
Ubiquitin C
Proteins
Protein Interaction Domains and Motifs
Substrates
Substrate Specificity
N-Methyl-D-Aspartate Receptors
Endoplasmic Reticulum
Neurons
Brain
Degradation

ASJC Scopus subject areas

  • Biochemistry

Cite this

A novel route for F-box protein-mediated ubiquitination links CHIP to glycoprotein quality control. / Nelson, Rick; Glenn, Kevin A.; Miller, Victor M.; Wen, Hsiang; Paulson, Henry L.

In: Journal of Biological Chemistry, Vol. 281, No. 29, 21.07.2006, p. 20242-20251.

Research output: Contribution to journalArticle

Nelson, Rick ; Glenn, Kevin A. ; Miller, Victor M. ; Wen, Hsiang ; Paulson, Henry L. / A novel route for F-box protein-mediated ubiquitination links CHIP to glycoprotein quality control. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 29. pp. 20242-20251.
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