High impact information on EDEM1

• Some of these (such as glucosidases I and II, calnexin, and calreticulin) have a central role in folding and retention, while others (such as alpha-mannosidases and EDEM) target unsalvageable glycoproteins for ER-associated degradation [1].
• These findings indicate that Derlin-2 and -3 provide the missing link between EDEM and p97 in the process of degrading misfolded glycoproteins [2].
• EDEM3, a soluble EDEM homolog, enhances glycoprotein endoplasmic reticulum-associated degradation and mannose trimming [3].
• Overexpression of EDEM3 also greatly stimulates mannose trimming not only from misfolded alpha1-AT null (Hong Kong) but also from total glycoproteins, in contrast to EDEM, which has no apparent alpha1,2-mannosidase activity [3].
• Importantly, vector-based RNA interference against EDEM, which leads to reduction of the cellular level of EDEM, decreased retrotranslocation of ricin A-chain to the cytosol [4].

Biological context of EDEM1

• Up-regulation of EDEM during ER stress may promote cell recovery by clearing the calnexin cycle and by accelerating ERAD of terminally misfolded polypeptides [5].
• 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 [5].
• However, transcriptional activation of the XBP-1 target gene EDEM (ER degradation-enhancing alpha-mannosidase-like protein, a protein degradation factor) was inhibited [6].

Anatomical context of EDEM1

• In conclusion, our results indicate that EDEM is involved in retrotranslocation of ricin from the ER to the cytosol [4].
• EDEM is involved in retrotranslocation of ricin from the endoplasmic reticulum to the cytosol [4].

Associations of EDEM1 with chemical compounds

• A novel stress-induced EDEM variant regulating endoplasmic reticulum-associated glycoprotein degradation [7].
• Although the luminal region of ER degradation enhancing alpha-mannosidase-like protein (EDEM) is similar to class I alpha1,2-mannosidases involved in N-glycan processing, EDEM did not have enzymatic activity [8].
• Coimmunoprecipitation studies revealed that ricin can interact with EDEM and with Sec61alpha, and both kifunensin and puromycin increase these interactions [4].
• In addition, ER mannosidase I inhibitor kifunensine and down-regulation of EDEM (ER degradation-enhancing alpha-mannosidase-like protein) also suppressed the degradation of Y611H mutant channels [9].

Regulatory relationships of EDEM1

• The ER stress-induced protein EDEM1 regulates disposal of folding-defective glycoproteins and has been described as a mannose-binding lectin [10].

Other interactions of EDEM1

• EDEM, a mannosidase-like chaperone, regulates the extraction of misfolded glycoproteins from the calnexin cycle [7].
• In this study, we characterize one of the EDEM homologs from Homo sapiens, which we have termed EDEM2 (C20orf31) [11].

References