Unglycosylation at Asn-633 made extracellular domain of E-cadherin folded incorrectly and arrested in endoplasmic reticulum, then sequentially degraded by ERAD

摘要: The human E-cadherin is a single transmembrane domain protein involved in Ca2+-dependent cell–cell adhesion. In previous study, we demonstrated that all of four potential N-glycosylation sites are occupied by N-glycans breast carcinoma cells vivo and the elimination N-glycan at Asn-633 dramatically affected expression made it degraded. this study investigated molecular mechanism E-cadherin, which lacks (M4), degradation role folding. We treated stably expressed M4 with MG123, DMM, respectively. Either MG132 or DMM could efficiently block E-cadherin. was recognized as substrate ERAD retro-translocated from ER lumen to cytoplasm p97. It observed ration binding calnexin significantly increased compared other variants, suggesting misfolded protein, though cytoplasmic associate β-catenin. Furthermore, found were modified immature high mannose type, not depart Golgi apparatus. conclusion, revealed essential for expression, folding trafficking.