ArticleThe Journal of biological chemistry2011
The role of monoubiquitination in endocytic degradation of human ether-a-go-go-related gene (hERG) channels under low K+ conditions.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Ubiquitination is involved in PKC-mediated degradation of cell surface Kv1.5 channels.The Journal of biological chemistry · 2024Article
- Spatacsin regulates directionality of lysosome trafficking by promoting the degradation of its partner AP5Z1.PLoS biology · 2023Article
- The cellular pathways that maintain the quality control and transport of diverse potassium channels.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- Insights of Endocytosis Signaling in Health and Disease.International journal of molecular sciences · 2023Review
- Multiubiquitination of TRPV4 reduces channel activity independent of surface localization.The Journal of biological chemistry · 2022Article
- E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy.Clinical and experimental immunology · 2021Review
- Review
- Mutation-specific peripheral and ER quality control of hERG channel cell-surface expression.Scientific reports · 2019Article
- Ubiquitination mediates Kv1.3 endocytosis as a mechanism for protein kinase C-dependent modulation.Scientific reports · 2017Article
- Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- hERG quality control and the long QT syndrome.The Journal of physiology · 2016Review
- Rab11-dependent Recycling of the Human Ether-a-go-go-related Gene (hERG) Channel.The Journal of biological chemistry · 2015Article
- Translational toxicology and rescue strategies of the hERG channel dysfunction: biochemical and molecular mechanistic aspects.Acta pharmacologica Sinica · 2014Review
- Solution structure of lysine-free (K0) ubiquitin.Protein science : a publication of the Protein Society · 2014Article
- Activation of the cAMP/PKA pathway induces UT-A1 urea transporter monoubiquitination and targets it for lysosomal degradation.American journal of physiology. Renal physiology · 2013Article
- Ubiquitination-dependent quality control of hERG K+ channel with acquired and inherited conformational defect at the plasma membrane.Molecular biology of the cell · 2013Article
- Regulation of the human ether-a-go-go-related gene (hERG) channel by Rab4 protein through neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2).The Journal of biological chemistry · 2013Article
- Article
- Article
- Cell surface expression of human ether-a-go-go-related gene (hERG) channels is regulated by caveolin-3 protein via the ubiquitin ligase Nedd4-2.The Journal of biological chemistry · 2012Article
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11 authors.
Funding
Abstract
A reduction in extracellular K(+) concentration ([K(+)](o)) causes cardiac arrhythmias and triggers internalization of the cardiac rapidly activating delayed rectifier potassium channel (I(Kr)) encoded by the human ether-a-go-go-related gene (hERG). We investigated the role of ubiquitin (Ub) in endocytic degradation of hERG channels stably expressed in HEK cells. Under low K(+) conditions, UbKO, a lysine-less mutant Ub that only supports monoubiquitination, preferentially interacted and selectively enhanced degradation of the mature hERG channels. Overexpression of Vps24 protein, also known as charged multivesicular body protein 3, significantly accelerated degradation of mature hERG channels, whereas knockdown of Vps24 impeded this process. Moreover, the lysosomal inhibitor bafilomycin A1 inhibited degradation of the internalized mature hERG channels. Thus, monoubiquitination directs mature hERG channels to degrade through the multivesicular body/lysosome pathway. Interestingly, the protease inhibitor lactacystin inhibited the low K(+)-induced hERG endocytosis and concomitantly led to an accumulation of monoubiquitinated mature hERG channels, suggesting that deubiquitination is also required for the endocytic degradation. Consistently, overexpression of the endosomal deubiquitinating enzyme signal transducing adaptor molecule-binding protein significantly accelerated whereas knockdown of endogenous signal transducing adaptor molecule-binding protein impeded degradation of the mature hERG channels under low K(+) conditions. Thus, monoubiquitin dynamically mediates endocytic degradation of mature hERG channels under low K(+) conditions.
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