ArticleThe Journal of cell biology2012
Aberrant substrate engagement of the ER translocon triggers degradation by the Hrd1 ubiquitin ligase.
Article in The Journal of cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 68 citations in OpenAlex.
- Comparative analysis of Cdc48-dependent proteolysis at the ER, mitochondria and chloroplasts.Nature communications · 2026Review
- Ubiquitin-conjugating enzyme membrane anchor Cue1 confers resistance to hygromycin B inmicroPublication biology · 2026Article
- The kinesin Kar3 is required for endoplasmic reticulum-associated degradation.Molecular biology of the cell · 2025Article
- Endoplasmic reticulum and inner nuclear membrane ubiquitin-conjugating enzymes Ubc6 and Ubc7 confer resistance to hygromycin B inmicroPublication biology · 2024Article
- Loss of transcriptional regulator of phospholipid biosynthesis alters post-translational modification of Sec61 translocon beta subunit Sbh1 inmicroPublication biology · 2024Article
- Lhs1 dependent ERAD is determined by transmembrane domain context.The Biochemical journal · 2023Article
- Methionine Restriction Impairs Degradation of a Protein that Aberrantly Engages the Endoplasmic Reticulum Translocon.microPublication biology · 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
- Therapeutic Uses of Bacterial Subunit Toxins.Toxins · 2021Review
- Characterization of constitutive ER-phagy of excess membrane proteins.PLoS genetics · 2020Article
- Overlapping function of Hrd1 and Ste24 in translocon quality control provides robust channel surveillance.The Journal of biological chemistry · 2020Article
- SGTA associates with nascent membrane protein precursors.EMBO reports · 2020Article
- Endoplasmic reticulum stress-regulated degradation of a translocon-associated protein is independent of integrated stress response transcription factor Gcn4p.microPublication biology · 2020Article
- A functional unfolded protein response is required for chronological aging in Saccharomyces cerevisiae.Current genetics · 2020Article
- Clearing Traffic Jams During Protein Translocation Across Membranes.Frontiers in cell and developmental biology · 2020Review
- Glucose concentration does not affect degradation of a protein that aberrantly engages the endoplasmic reticulum translocon.microPublication biology · 2020Article
- Endoplasmic reticulum stress differentially inhibits endoplasmic reticulum and inner nuclear membrane protein quality control degradation pathways.The Journal of biological chemistry · 2019Article
- Regulation of inner nuclear membrane associated protein degradation.Nucleus (Austin, Tex.) · 2019Review
- Degradation of integral membrane proteins modified with the photosensitive degron module requires the cytosolic endoplasmic reticulum-associated degradation pathway.Molecular biology of the cell · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Little is known about quality control of proteins that aberrantly or persistently engage the endoplasmic reticulum (ER)-localized translocon en route to membrane localization or the secretory pathway. Hrd1 and Doa10, the primary ubiquitin ligases that function in ER-associated degradation (ERAD) in yeast, target distinct subsets of misfolded or otherwise abnormal proteins based primarily on degradation signal (degron) location. We report the surprising observation that fusing Deg1, a cytoplasmic degron normally recognized by Doa10, to the Sec62 membrane protein rendered the protein a Hrd1 substrate. Hrd1-dependent degradation occurred when Deg1-Sec62 aberrantly engaged the Sec61 translocon channel and underwent topological rearrangement. Mutations that prevent translocon engagement caused a reversion to Doa10-dependent degradation. Similarly, a variant of apolipoprotein B, a protein known to be cotranslocationally targeted for proteasomal degradation, was also a Hrd1 substrate. Hrd1 therefore likely plays a general role in targeting proteins that persistently associate with and potentially obstruct the translocon.
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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.