Earticle

초록

영어

Misfolded and mis-assembled glycoproteins are retained in the endoplasmic reticulum (ER) where they are exposed to the protein folding machinery and protein quality control. The UPR (Unfoled Protein Response) is activated in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum. Eventually, misfolded and mis-assembled glycoproteins are targeted for degradation by a process called ER-associated protein degradation (ERAD). EDEM1 is an ERAD component that recognizes misfolded luminal glycoproteins and is routing them for dislocation to the cytosol. This is classically followed by their degradation. Although EDEM1 was initially proposed to be lectin–like and to react with Man8GlcNAc2 oligosaccharides of glycoproteins, its complex mode of interaction with substrates has become clear only recently. However, still very little is known about the turnover and degradation mechanism of EDEM1 and how this relates to the fate of its substrates. We already reported that EDEM1 becomes rapidly degraded and that this occurs by basal autophagy. Here, we provide detailed insight into the mechanism by which EDEM1 becomes degraded. After its dislocation to the cytosol, EDEM1 is apparently making complexes with the selective autophagy receptors p62, NBR1 and Alfy. We observed co-distribution of EDEM1 and selective autophagy receptors by double or triple confocal laser scanning immunofluorescence. By quantifying the relationship of EDEM1 and the selective autophagy receptors as visualized by confocal laser scanning immunofluorescence, dramatical changes were observed in HepG2 cells following inhibition of autophagy by wortmannin treatment. These changes were fully reversible upon wortmannin wash-out. In addition, we observed its ubiquitination after dislocation to the cytosol. This demonstrates that the ERAD component EDEM1 itself undergoes ERAD involving selective autophagy

저자

• Sujin Park [ Department of Integrated OMICS for Biomedical Science, WCU Program of Yonsei University Graduate School, Yonsei University ]
• Insook Jang [ Department of Integrated OMICS for Biomedical Science, WCU Program of Yonsei University Graduate School, Yonsei University ]
• Jin Won Cho [ Department of Integrated OMICS for Biomedical Science, WCU Program of Yonsei University Graduate School, Yonsei University ]
• Jürgen Roth [ Department of Integrated OMICS for Biomedical Science, WCU Program of Yonsei University Graduate School, Yonsei University ]

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간행물

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• 간행물명

  한국당과학회 학술대회

• 간기

  연간

• 수록기간

  2006~2022

• 십진분류

  KDC 517 DDC 614