E3 ubiquitin ligase that recognizes sugar chains.

N-glycosylation of proteins in the endoplasmic reticulum (ER) has a central role in protein quality control. Here we report that N-glycan serves as a signal for degradation by the Skp1-Cullin1-Fbx2-Roc1 (SCF(Fbx2)) ubiquitin ligase complex. The F-box protein Fbx2 (ref. 4) binds specifically to proteins attached to N-linked high-mannose oligosaccharides and ...
subsequently contributes to ubiquitination of N-glycosylated proteins. Pre-integrin beta 1 is a target of Fbx2; these two proteins interact in the cytosol after inhibition of the proteasome. In addition, expression of the mutant Fbx2 Delta F, which lacks the F-box domain that is essential for forming the SCF complex, appreciably blocks degradation of typical substrates of the ER-associated degradation pathway. Our results indicate that SCF(Fbx2) ubiquitinates N-glycosylated proteins that are translocated from the ER to the cytosol by the quality control mechanism.
Mesh Terms:
Animals, Antigens, CD29, Cell Line, Cysteine Endopeptidases, Cystic Fibrosis Transmembrane Conductance Regulator, Endoplasmic Reticulum, Glycoproteins, Glycosylation, Humans, Leupeptins, Ligases, Macromolecular Substances, Mannose, Mice, Multienzyme Complexes, Polysaccharides, Proteasome Endopeptidase Complex, Protein Binding, Protein Precursors, Ribonucleases, Substrate Specificity, Transfection, Ubiquitin, Ubiquitin-Protein Ligases, alpha-Fetoproteins
Nature
Date: Jul. 25, 2002
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