ArticlePloS one2012
Tyrosinase degradation is prevented when EDEM1 lacks the intrinsically disordered region.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 44 citations in OpenAlex.
- Turnover of EDEM1, an ERAD-enhancing factor, is mediated by multiple degradation routes.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Targeting EDEM protects against ER stress and improves development and survival in C. elegans.PLoS genetics · 2022Article
- EDEM1 Regulates Amyloid Precursor Protein (APP) Metabolism and Amyloid-β Production.International journal of molecular sciences · 2021Article
- Clamping, bending, and twisting inter-domain motions in the misfold-recognizing portion of UDP-glucose: Glycoprotein glucosyltransferase.Structure (London, England : 1993) · 2021Article
- EDEM3 Domains Cooperate to Perform Its Overall Cell Functioning.International journal of molecular sciences · 2021Article
- Review
- EDEM1 Drives Misfolded Protein Degradation via ERAD and Exploits ER-Phagy as Back-Up Mechanism When ERAD Is Impaired.International journal of molecular sciences · 2020Article
- The Crucial Role of Demannosylating Asparagine-Linked Glycans in ERADicating Misfolded Glycoproteins in the Endoplasmic Reticulum.Frontiers in plant science · 2020Review
- Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.International journal of molecular sciences · 2019Article
- Modulation of ERQC and ERAD: A Broad-Spectrum Spanner in the Works of Cancer Cells?Journal of oncology · 2019Review
- Article
- EDEM1's mannosidase-like domain binds ERAD client proteins in a redox-sensitive manner and possesses catalytic activity.The Journal of biological chemistry · 2018Article
- Mannosidase activity of EDEM1 and EDEM2 depends on an unfolded state of their glycoprotein substrates.Communications biology · 2018Article
- Roles of the C-terminal domains of topoisomerase IIα and topoisomerase IIβ in regulation of the decatenation checkpoint.Nucleic acids research · 2017Article
- Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells.Oncotarget · 2017Article
- Exposure to Melan-A/MART-126-35 tumor epitope specific CD8(+)T cells reveals immune escape by affecting the ubiquitin-proteasome system (UPS).Scientific reports · 2016Article
- The Role of Lectin-Carbohydrate Interactions in the Regulation of ER-Associated Protein Degradation.Molecules (Basel, Switzerland) · 2015Review
- Article
- A high-throughput screen identifies miRNA inhibitors regulating lung cancer cell survival and response to paclitaxel.RNA biology · 2013Article
- A shared endoplasmic reticulum-associated degradation pathway involving the EDEM1 protein for glycosylated and nonglycosylated proteins.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EDEM1 is a mannosidase-like protein that recruits misfolded glycoproteins from the calnexin/calreticulin folding cycle to downstream endoplasmic reticulum associated degradation (ERAD) pathway. Here, we investigate the role of EDEM1 in the processing of tyrosinase, a tumour antigen overexpressed in melanoma cells. First, we analyzed and modeled EDEM1 major domains. The homology model raised on the crystal structures of human and Saccharomyces cerevisiae ER class I α1,2-mannosidases reveals that the major mannosidase domain located between aminoacids 121-598 fits with high accuracy. We have further identified an N-terminal region located between aminoacids 40-119, predicted to be intrinsically disordered (ID) and susceptible to adopt multiple conformations, hence facilitating protein-protein interactions. To investigate these two domains we have constructed an EDEM1 deletion mutant lacking the ID region and a triple mutant disrupting the glycan-binding domain and analyzed their association with tyrosinase. Tyrosinase is a glycoprotein partly degraded endogenously by ERAD and the ubiquitin proteasomal system. We found that the degradation of wild type and misfolded tyrosinase was enhanced when EDEM1 was overexpressed. Glycosylated and non-glycosylated mutants co-immunoprecipitated with EDEM1 even in the absence of its intact mannosidase-like domain, but not when the ID region was deleted. In contrast, calnexin and SEL 1L associated with the deletion mutant. Our data suggest that the ID region identified in the N-terminal end of EDEM1 is involved in the binding of glycosylated and non-glycosylated misfolded proteins. Accelerating tyrosinase degradation by EDEM1 overexpression may lead to an efficient antigen presentation and enhanced elimination of melanoma cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.