ArticleThe Journal of biological chemistry2017
Bag1 Co-chaperone Promotes TRC8 E3 Ligase-dependent Degradation of Misfolded Human Ether a Go-Go-related Gene (hERG) Potassium Channels.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- A Bioinformatic Analysis of BAG Protein Interactors and Pathways in Alzheimer's and Parkinson's Disease.Journal of molecular neuroscience : MN · 2026Review
- Recent insights into HSP70: proteostasis and beyond.Frontiers in molecular biosciences · 2026Review
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- The proteostasis interactomes of trafficking-deficient variants of the voltage-gated potassium channel KThe Journal of biological chemistry · 2024Article
- Advances in the study of protein folding and endoplasmic reticulum-associated degradation in mammal cells.Journal of Zhejiang University. Science. B · 2024Review
- The cellular pathways that maintain the quality control and transport of diverse potassium channels.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- Reversible protein assemblies in the proteostasis network in health and disease.Frontiers in molecular biosciences · 2023Review
- Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities.MedComm · 2022Review
- A chemical probe for BAG1 targets androgen receptor-positive prostate cancer through oxidative stress signaling pathway.iScience · 2022Article
- Cytosolic protein quality control machinery: Interactions of Hsp70 with a network of co-chaperones and substrates.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Interactome analysis of Bag-1 isoforms reveals novel interaction partners in endoplasmic reticulum-associated degradation.PloS one · 2021Article
- Co-Chaperones in Targeting and Delivery of Misfolded Proteins to the 26S Proteasome.Biomolecules · 2020Review
- Thioridazine Induces Cardiotoxicity via Reactive Oxygen Species-Mediated hERG Channel Deficiency and L-Type Calcium Channel Activation.Oxidative medicine and cellular longevity · 2020Article
- BCL2-ASSOCIATED ATHANOGENE4 Regulates the KAT1 Potassium Channel and Controls Stomatal Movement.Plant physiology · 2019Article
- Hsp70 molecular chaperones: multifunctional allosteric holding and unfolding machines.The Biochemical journal · 2019Review
- Mutation-specific peripheral and ER quality control of hERG channel cell-surface expression.Scientific reports · 2019Article
- Trafficking of the human ether-a-go-go-related gene (hERG) potassium channel is regulated by the ubiquitin ligase rififylin (RFFL).The Journal of biological chemistry · 2019Article
- Silencing of the Hsp70-specific nucleotide-exchange factor BAG3 corrects the F508del-CFTR variant by restoring autophagy.The Journal of biological chemistry · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Cardiac long QT syndrome type 2 is caused by mutations in the human ether a go-go-related gene (hERG) potassium channel, many of which cause misfolding and degradation at the endoplasmic reticulum instead of normal trafficking to the cell surface. The Hsc70/Hsp70 chaperones assist the folding of the hERG cytosolic domains. Here, we demonstrate that the Hsp70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at the endoplasmic reticulum to regulate hERG levels and channel activity. Dissociation of hERG complexes containing Hsp70 and the E3 ubiquitin ligase CHIP requires the interaction of Bag1 with Hsp70, but this does not involve the Bag1 ubiquitin-like domain. The interaction with Bag1 then shifts hERG degradation to the membrane-anchored E3 ligase TRC8 and its E2-conjugating enzyme Ube2g2, as determined by siRNA screening. TRC8 interacts through the transmembrane region with hERG and decreases hERG functional expression. TRC8 also mediates degradation of the misfolded hERG-G601S disease mutant, but pharmacological stabilization of the mutant structure prevents degradation. Our results identify TRC8 as a previously unknown Hsp70-independent quality control E3 ligase for hERG.
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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.