ArticleBMC cell biology2015
Hydrophobicity of protein determinants influences the recognition of substrates by EDEM1 and EDEM2 in human cells.
Article in BMC cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 35 citations in OpenAlex.
- N-glycan-dependent protein maturation and quality control in the ER.Nature reviews. Molecular cell biology · 2025Review
- ER-to-lysosome-associated degradation acts as failsafe mechanism upon ERAD dysfunction.EMBO reports · 2024Article
- EDEM1 Regulates Amyloid Precursor Protein (APP) Metabolism and Amyloid-β Production.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
- Disposing of misfolded ER proteins: A troubled substrate's way out of the ER.Molecular and cellular endocrinology · 2020Review
- The Crucial Role of Demannosylating Asparagine-Linked Glycans in ERADicating Misfolded Glycoproteins in the Endoplasmic Reticulum.Frontiers in plant science · 2020Review
- Review
- Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process.International journal of molecular sciences · 2019Review
- Modulation of ERQC and ERAD: A Broad-Spectrum Spanner in the Works of Cancer Cells?Journal of oncology · 2019Review
- 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
- Chaperone activity of human small heat shock protein-GST fusion proteins.Cell stress & chaperones · 2017Article
- The Role of Lectin-Carbohydrate Interactions in the Regulation of ER-Associated Protein Degradation.Molecules (Basel, Switzerland) · 2015Review
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. It has previously been demonstrated that EDEM1 and EDEM2 binding does not require the trimming of substrate glycans or even ERAD substrate glycosylation, thus suggesting that both chaperones probably recognize misfolded regions of aberrant proteins.
resultsIn this work, we focused on the substrate recognition by EDEM1 and EDEM2, asking whether hydrophobicity of protein determinants might be important for these interactions in human cells. In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. Mutations in the hydrophobic regions of these proteins allowed us to obtain mutated forms with increased and decreased hydrophobicity.
conclusionsOur data provide the first evidence that recognition of ERAD substrates by EDEM1 and EDEM2 might be determined by a sufficiently high hydrophobicity of protein determinants. Moreover, EDEM proteins can bind hydrophobic transmembrane regions of misfolded ERAD substrates. These data contribute to the general understanding of the regulation of ERAD in mammalian cells.
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