The mechanisms that determine how folding attempts are interrupted to target folding-incompetent proteins for endoplasmic reticulum-associated degradation (ERAD) are poorly defined. Here the alpha-mannosidase I-like protein EDEM was shown to extract misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle. EDEM overexpression resulted in faster release of folding-incompetent proteins from the calnexin cycle and earlier onset of degradation, whereas EDEM down-regulation prolonged folding attempts and delayed ERAD. Up-regulation of EDEM during ER stress may promote cell recovery by clearing the calnexin cycle and by accelerating ERAD of terminally misfolded polypeptides.
机构:Nagoya Univ, Grad Sch Sci, Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, Japan
Nakatsukasa, K
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Nishikawa, S
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机构:Nagoya Univ, Grad Sch Sci, Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, Japan
Nishikawa, S
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Hosokawa, N
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机构:Nagoya Univ, Grad Sch Sci, Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, Japan
Hosokawa, N
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Nagata, K
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机构:Nagoya Univ, Grad Sch Sci, Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, Japan
Nagata, K
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Endo, T
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Nagoya Univ, Grad Sch Sci, Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, JapanNagoya Univ, Grad Sch Sci, Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, Japan
机构:Nagoya Univ, Grad Sch Sci, Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, Japan
Nakatsukasa, K
;
Nishikawa, S
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机构:Nagoya Univ, Grad Sch Sci, Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, Japan
Nishikawa, S
;
Hosokawa, N
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机构:Nagoya Univ, Grad Sch Sci, Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, Japan
Hosokawa, N
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Nagata, K
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机构:Nagoya Univ, Grad Sch Sci, Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, Japan
Nagata, K
;
Endo, T
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Nagoya Univ, Grad Sch Sci, Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, JapanNagoya Univ, Grad Sch Sci, Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, Japan