ArticleMolecular biology of the cell2015
gp78 functions downstream of Hrd1 to promote degradation of misfolded proteins of the endoplasmic reticulum.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- Enhancing Proteasome Activity in T Cells Alleviates Exhaustion and Improves Antitumor Immunity.Cancer research · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- A UBH-UBX module amplifies p97/VCP's unfolding power to facilitate protein extraction and degradation.Nature communications · 2025Article
- MYC affects mitochondrial function in IgA nephropathy by promoting the degradation of MFN1 through HRD1.Immunologic research · 2025Article
- The p97 ATPase and its adaptor UBXD8 maintain peroxisome pools by preventing pexophagy.The Journal of cell biology · 2025Article
- NEMF-mediated CAT tailing facilitates translocation-associated quality control.The Journal of cell biology · 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 p97-UBXD8 complex maintains peroxisome abundance by suppressing pexophagy.bioRxiv : the preprint server for biology · 2024Article
- Turnover of EDEM1, an ERAD-enhancing factor, is mediated by multiple degradation routes.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Mechanisms of substrate processing during ER-associated protein degradation.Nature reviews. Molecular cell biology · 2023Review
- Mechanism and Role of Endoplasmic Reticulum Stress in Osteosarcoma.Biomolecules · 2022Review
- Modulating the Ubiquitin-Proteasome System: A Therapeutic Strategy for Autoimmune Diseases.Cells · 2022Review
- The GR-gp78 Pathway is involved in Hepatic Lipid Accumulation Induced by Overexpression of 11β-HSD1.International journal of biological sciences · 2022Article
- 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
- Cargo Recognition and Function of Selective Autophagy Receptors in Plants.International journal of molecular sciences · 2021Review
- Calnexin mediates the maturation of GPI-anchors through ER retention.The Journal of biological chemistry · 2020Article
- Unraveling the regulatory role of endoplasmic-reticulum-associated degradation in tumor immunity.Critical reviews in biochemistry and molecular biology · 2020Review
- Article
- Disposing of misfolded ER proteins: A troubled substrate's way out of the ER.Molecular and cellular endocrinology · 2020Review
- ER-associated degradation in health and disease - from substrate to organism.Journal of cell science · 2019Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Eukaryotic cells eliminate misfolded proteins from the endoplasmic reticulum (ER) via a conserved process termed ER-associated degradation (ERAD). Central regulators of the ERAD system are membrane-bound ubiquitin ligases, which are thought to channel misfolded proteins through the ER membrane during retrotranslocation. Hrd1 and gp78 are mammalian ubiquitin ligases homologous to Hrd1p, an ubiquitin ligase essential for ERAD in Saccharomyces cerevisiae. However, the functional relevance of these proteins to Hrd1p is unclear. In this paper, we characterize the gp78-containing ubiquitin ligase complex and define its functional interplay with Hrd1 using biochemical and recently developed CRISPR-based genetic tools. Our data show that transient inactivation of the gp78 complex by short hairpin RNA-mediated gene silencing causes significant stabilization of both luminal and membrane ERAD substrates, but unlike Hrd1, which plays an essential role in retrotranslocation and ubiquitination of these ERAD substrates, knockdown of gp78 does not affect either of these processes. Instead, gp78 appears to act downstream of Hrd1 to promote ERAD via cooperation with the BAG6 chaperone complex. We conclude that the Hrd1 complex forms an essential retrotranslocation module that is evolutionarily conserved, but the mammalian ERAD system uses additional ubiquitin ligases to assist Hrd1 during retrotranslocation.
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