Lectin-like ERAD players in ER and cytosol.
Protein quality control in the endoplasmic reticulum (ER) is an elaborate process conserved from yeast to mammals, ensuring that only newly synthesized proteins with correct conformations in the ER are sorted further into the secretory pathway. It is well known that high-mannose type N-glycans are involved in protein-folding events. In the quality control process, proteins that fail to achieve proper folding or proper assembly are degraded in a process known as ER-associated degradation (ERAD). The ERAD pathway comprises multiple steps including substrate recognition and targeting to the retro-translocation machinery, retrotranslocation from the ER into the cytosol, and proteasomal degradation through ubiquitination. Recent studies have documented the important roles of sugar-recognition (lectin-type) molecules for trimmed high-mannose type N-glycans and glycosidases in the ERAD pathways in both ER and cytosol. In this review, we discuss a fundamental system that monitors glycoprotein folding in the ER and the unique roles of the sugar-recognizing ubiquitin ligase and peptide:N-glycanase (PNGase) in the cytosolic ERAD pathway.
Yoshida
Yukiko
Y
Laboratory of Frontier Science, The Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan. yoshida-yk@igakuken.or.jp
Tanaka
Keiji
K
D002240:Carbohydrate Sequence; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D044783:F-Box Proteins; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008361:Mannosidases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C486654:EDEM1 protein, human; C531192:ERLEC1 protein, human; D044783:F-Box Proteins; C485508:FBXO2 protein, human; D037102:Lectins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C098898:OS9 protein, human; D011134:Polysaccharides; D029701:Saccharomyces cerevisiae Proteins; C495027:Yos9 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; C434527:MNL1 protein, S cerevisiae; D008361:Mannosidases; D046988:Proteasome Endopeptidase Complex; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase