ArticleThe Journal of biological chemistry2011
An unusual transmembrane helix in the endoplasmic reticulum ubiquitin ligase Doa10 modulates degradation of its cognate E2 enzyme.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Proteome analyses reveal endoplasmic reticulum stress-induced changes in protein abundance associated with Ube2j2 deficiency in human cell culture.G3 (Bethesda, Md.) · 2026Article
- Substrate recognition mechanism of the endoplasmic reticulum-associated ubiquitin ligase Doa10.Nature communications · 2024Article
- Substrate recognition mechanism of the endoplasmic reticulum-associated ubiquitin ligase Doa10.bioRxiv : the preprint server for biology · 2024Article
- Mechanisms of substrate processing during ER-associated protein degradation.Nature reviews. Molecular cell biology · 2023Review
- Nt-acetylation-independent turnover of SQUALENE EPOXIDASE 1 by Arabidopsis DOA10-like E3 ligases.Plant physiology · 2023Article
- The Brucella abortus Type IV Effector BspA Inhibits MARCH6-Dependent ERAD To Promote Intracellular Growth.Infection and immunity · 2023Article
- Characterization of endoplasmic reticulum-associated degradation in the human fungal pathogenPeerJ · 2023Article
- Elements of the ERAD ubiquitin ligase Doa10 regulating sequential poly-ubiquitylation of its targets.iScience · 2022Article
- Ubiquitin Ligase Redundancy and Nuclear-Cytoplasmic Localization in Yeast Protein Quality Control.Biomolecules · 2021Review
- Ubiquitination in the ERAD Process.International journal of molecular sciences · 2020Review
- Ubiquitin-dependent protein degradation at the endoplasmic reticulum and nuclear envelope.Seminars in cell & developmental biology · 2019Review
- A Conserved C-terminal Element in the Yeast Doa10 and Human MARCH6 Ubiquitin Ligases Required for Selective Substrate Degradation.The Journal of biological chemistry · 2016Article
- Protein quality and quantity control at the yeast ER.Oncotarget · 2015Article
- The yeast ERAD-C ubiquitin ligase Doa10 recognizes an intramembrane degron.The Journal of cell biology · 2015Article
- Distinct activation of an E2 ubiquitin-conjugating enzyme by its cognate E3 ligases.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- ERAD and how viruses exploit it.Frontiers in microbiology · 2014Review
- Ubiquitin conjugation triggers misfolded protein sequestration into quality control foci when Hsp70 chaperone levels are limiting.Molecular biology of the cell · 2013Article
- N-terminal acetylation of the yeast Derlin Der1 is essential for Hrd1 ubiquitin-ligase activity toward luminal ER substrates.Molecular biology of the cell · 2013Article
- The SUD1 gene encodes a putative E3 ubiquitin ligase and is a positive regulator of 3-hydroxy-3-methylglutaryl coenzyme a reductase activity in Arabidopsis.The Plant cell · 2013Article
- Mutation of an Arabidopsis NatB N-alpha-terminal acetylation complex component causes pleiotropic developmental defects.PloS one · 2013Article
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
In the endoplasmic reticulum (ER), nascent membrane and secreted proteins that are misfolded are retrotranslocated into the cytosol and degraded by the proteasome. For most ER-associated degradation (ERAD) substrates, ubiquitylation is essential for both their retrotranslocation and degradation. Yeast Doa10 is a polytopic membrane ubiquitin ligase (E3) that along with its cognate ubiquitin-conjugating enzymes (E2s), Ubc7 and the C-terminally membrane-anchored Ubc6, makes a major contribution to ER-associated degradation. Ubc6 is also a substrate of Doa10. One highly conserved Doa10 element, the uncharacterized ~130-residue TEB4-Doa10 domain, includes three transmembrane helices (TMs). We find that the first of these, TM5, includes an absolutely conserved ΦPΦXXG motif that is required for Doa10 function, as well as highly conserved negatively charged glutamate and aspartate residues. The conservative exchange of the TM5 glutamate to aspartate (doa10-E633D) results in complete stabilization of Ubc6 but has little if any effect on other substrates. Unexpectedly, mutating the glutamate to glutamine (doa10-E633Q) specifically accelerates Ubc6 degradation by ~5-fold. Other substrates are weakly stabilized in doa10-E633Q cells, consistent with reduced Ubc6 levels. Notably, catalytically inactive ubc6-C87A is degraded in doa10-E633Q but not wild-type cells, but an active version of Ubc6 is required in trans. Fusion of the Ubc6 TM to a soluble protein yields a protein that is degraded in a doa10-E633Q-dependent manner, whereas fusion of the C-terminal TM from an unrelated protein does not. These results suggest that the TEB4-Doa10 domain regulates Doa10 association with the Ubc6 membrane anchor, thereby controlling the degradation rate of the E2.
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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.