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.
Yoshida
Yukiko
Y
Tokyo Metropolitan Institute of Medical Science, 3-18-22, Hon-komagome, Bunkyo-ku, Tokyo 113-8613, Japan. yyosida@rinshoken.or.jp
Adachi
Eru
E
Fukiya
Kanako
K
Iwai
Kazuhiro
K
Tanaka
Keiji
K
D000251:Adenosine Triphosphatases; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009844:Oligosaccharides / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D013379:Substrate Specificity; D025801:Ubiquitin / Q000378:metabolism; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D006023:Glycoproteins; D039641:Integrin beta Chains; D009844:Oligosaccharides; D011134:Polysaccharides; D025801:Ubiquitin; D044843:SKP Cullin F-Box Protein Ligases; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse
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