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. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
CITATION STYLE
Nelson, R. F., Glenn, K. A., Miller, V. M., Wen, H., & Paulson, H. L. (2006). A novel route for F-box protein-mediated ubiquitination links CHIP to glycoprotein quality control. Journal of Biological Chemistry, 281(29), 20242–20251. https://doi.org/10.1074/jbc.M602423200
Mendeley helps you to discover research relevant for your work.