ArticleThe Journal of biological chemistry2016
A Conserved C-terminal Element in the Yeast Doa10 and Human MARCH6 Ubiquitin Ligases Required for Selective Substrate Degradation.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Squalene Epoxidase: Its Regulations and Links with Cancers.International journal of molecular sciences · 2024Pooled it
- Neutrophil extracellular traps as biomarkers for predicting prognosis and chemotherapy response in colorectal cancer.Scientific reports · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Determinants of chemoselectivity in ubiquitination by the J2 family of ubiquitin-conjugating enzymes.The EMBO journal · 2024Article
- Role of MARCH E3 ubiquitin ligases in cancer development.Cancer metastasis reviews · 2024Review
- Substrate recognition mechanism of the endoplasmic reticulum-associated ubiquitin ligase Doa10.Nature communications · 2024Article
- Doa10/MARCH6 architecture interconnects E3 ligase activity with lipid-binding transmembrane channel to regulate SQLE.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
- Profiling proteomic responses to hexokinase-II depletion in terpene-producingEngineering microbiology · 2023Article
- Characterization of endoplasmic reticulum-associated degradation in the human fungal pathogenPeerJ · 2023Article
- Endoplasmic Reticulum-Associated Protein Degradation.Cold Spring Harbor perspectives in biology · 2022Review
- Elements of the ERAD ubiquitin ligase Doa10 regulating sequential poly-ubiquitylation of its targets.iScience · 2022Article
- The MARCHF6 E3 ubiquitin ligase acts as an NADPH sensor for the regulation of ferroptosis.Nature cell biology · 2022Article
- Order through destruction: how ER-associated protein degradation contributes to organelle homeostasis.The EMBO journal · 2022Review
- USP5 enhances SGTA mediated protein quality control.PloS one · 2022Article
- Familial adult myoclonic epilepsy (FAME): clinical features, molecular characteristics, pathophysiological aspects and diagnostic work-up.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2021Article
- How Is the Fidelity of Proteins Ensured in Terms of Both Quality and Quantity at the Endoplasmic Reticulum? Mechanistic Insights into E3 Ubiquitin Ligases.International journal of molecular sciences · 2021Review
- The Degron Architecture of Squalene Monooxygenase and How Specific Lipids Calibrate Levels of This Key Cholesterol Synthesis Enzyme.Advances in experimental medicine and biology · 2021Article
- MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9.International journal of biological sciences · 2021Article
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Specific proteins are modified by ubiquitin at the endoplasmic reticulum (ER) and are degraded by the proteasome, a process referred to as ER-associated protein degradation. In Saccharomyces cerevisiae, two principal ER-associated protein degradation ubiquitin ligases (E3s) reside in the ER membrane, Doa10 and Hrd1. The membrane-embedded Doa10 functions in the degradation of substrates in the ER membrane, nuclear envelope, cytoplasm, and nucleoplasm. How most E3 ligases, including Doa10, recognize their protein substrates remains poorly understood. Here we describe a previously unappreciated but highly conserved C-terminal element (CTE) in Doa10; this cytosolically disposed 16-residue motif follows the final transmembrane helix. A conserved CTE asparagine residue is required for ubiquitylation and degradation of a subset of Doa10 substrates. Such selectivity suggests that the Doa10 CTE is involved in substrate discrimination and not general ligase function. Functional conservation of the CTE was investigated in the human ortholog of Doa10, MARCH6 (TEB4), by analyzing MARCH6 autoregulation of its own degradation. Mutation of the conserved Asn residue (N890A) in the MARCH6 CTE stabilized the normally short lived enzyme to the same degree as a catalytically inactivating mutation (C9A). We also report the localization of endogenous MARCH6 to the ER using epitope tagging of the genomic MARCH6 locus by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing. These localization and CTE analyses support the inference that MARCH6 and Doa10 are functionally similar. Moreover, our results with the yeast enzyme suggest that the CTE is involved in the recognition and/or ubiquitylation of specific protein substrates.
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