Glycoprotein-specific ubiquitin ligases recognize N-glycans in unfolded substrates.
Misfolded or unassembled polypeptides in the endoplasmic reticulum (ER) are retro-translocated into the cytosol and degraded by the ubiquitin-proteasome system. We reported previously that the SCF(Fbs1,2) ubiquitin-ligase complexes that contribute to ubiquitination of glycoproteins are involved in the ER-associated degradation pathway. Here we investigated how the SCF(Fbs1,2) complexes interact with ... unfolded glycoproteins. The SCF(Fbs1) complex was associated with p97/VCP AAA ATPase and bound to integrin-beta1, one of the SCF(Fbs1) substrates, in the cytosol in a manner dependent on p97 ATPase activity. Both Fbs1 and Fbs2 proteins interacted with denatured glycoproteins, which were modified with not only high-mannose but also complex-type oligosaccharides, more efficiently than native proteins. Given that Fbs proteins interact with innermost chitobiose in N-glycans, we propose that Fbs proteins distinguish native from unfolded glycoproteins by sensing the exposed chitobiose structure.
Mesh Terms:
Adenosine Triphosphatases, Animals, Cell Cycle Proteins, Cell Line, Glycoproteins, Humans, Integrin beta Chains, Mice, Oligosaccharides, Polysaccharides, Protein Binding, Protein Denaturation, Protein Folding, SKP Cullin F-Box Protein Ligases, Substrate Specificity, Ubiquitin
Adenosine Triphosphatases, Animals, Cell Cycle Proteins, Cell Line, Glycoproteins, Humans, Integrin beta Chains, Mice, Oligosaccharides, Polysaccharides, Protein Binding, Protein Denaturation, Protein Folding, SKP Cullin F-Box Protein Ligases, Substrate Specificity, Ubiquitin
EMBO Rep.
Date: Mar. 01, 2005
PubMed ID: 15723043
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