ArticleEMBO reports2018
MARCH6 and TRC8 facilitate the quality control of cytosolic and tail-anchored proteins.
Article in EMBO reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 81 citations in OpenAlex.
- RNF185 destabilizes specific membrane proteins that span all ERAD branches.bioRxiv : the preprint server for biology · 2026Article
- Review
- Dimeric architecture and membrane thinning govern substrate recognition by human signal peptide peptidase.Research square · 2026Article
- Mitochondria serve as a holdout compartment for aggregation-prone proteins hindering efficient degradation.Nature communications · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- UBE2J2 sensitizes the ERAD ubiquitination cascade to changes in membrane lipid saturation.Nature communications · 2025Article
- A nanobody that binds to the backside of the ubiquitin conjugating enzyme Ube2G2 differentially affects interactions with its partner E3 Ligases.Communications biology · 2025Article
- The DNase TREX1 is a substrate of the intramembrane protease SPP with implications for disease pathogenesis.Cellular and molecular life sciences : CMLS · 2025Article
- Topology surveillance of the lanosterol demethylase CYP51A1 by signal peptide peptidase.Journal of cell science · 2024Article
- The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi.Nature communications · 2024Article
- AUP1 Regulates the Endoplasmic Reticulum-Associated Degradation and Polyubiquitination of NKCC2.Cells · 2024Article
- Doa10/MARCH6 architecture interconnects E3 ligase activity with lipid-binding transmembrane channel to regulate SQLE.Nature communications · 2024Article
- Parallel CRISPR-Cas9 screens identify mechanisms of PLIN2 and lipid droplet regulation.Developmental cell · 2023Article
- A HIF independent oxygen-sensitive pathway for controlling cholesterol synthesis.Nature communications · 2023Article
- ALS-linked CCNF variant disrupts motor neuron ubiquitin homeostasis.Human molecular genetics · 2023Article
- The Endoplasmic Reticulum and the Fidelity of Nascent Protein Localization.Cold Spring Harbor perspectives in biology · 2023Review
- Article
- Endoplasmic Reticulum-Associated Protein Degradation.Cold Spring Harbor perspectives in biology · 2022Review
- ATP13A1 prevents ERAD of folding-competent mislocalized and misoriented proteins.Molecular cell · 2022Article
- The MARCHF6 E3 ubiquitin ligase acts as an NADPH sensor for the regulation of ferroptosis.Nature cell biology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Misfolded or damaged proteins are typically targeted for destruction by proteasome-mediated degradation, but the mammalian ubiquitin machinery involved is incompletely understood. Here, using forward genetic screens in human cells, we find that the proteasome-mediated degradation of the soluble misfolded reporter, mCherry-CL1, involves two ER-resident E3 ligases, MARCH6 and TRC8. mCherry-CL1 degradation is routed via the ER membrane and dependent on the hydrophobicity of the substrate, with complete stabilisation only observed in double knockout MARCH6/TRC8 cells. To identify a more physiological correlate, we used quantitative mass spectrometry and found that TRC8 and MARCH6 depletion altered the turnover of the tail-anchored protein heme oxygenase-1 (HO-1). These E3 ligases associate with the intramembrane cleaving signal peptide peptidase (SPP) and facilitate the degradation of HO-1 following intramembrane proteolysis. Our results highlight how ER-resident ligases may target the same substrates, but work independently of each other, to optimise the protein quality control of selected soluble and tail-anchored proteins.
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Registered trials
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.