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Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels
Anoctamin-1 (ANO1) (TMEM16A) is a calcium-activated chloride channel that plays critical roles in diverse physiological processes, such as sensory transduction and epithelial secretion. ANO1 levels have been shown to be altered under physiological and pathological conditions, although the molecular...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191318/ https://www.ncbi.nlm.nih.gov/pubmed/33957127 http://dx.doi.org/10.1016/j.jbc.2021.100738 |
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author | Cao, Xu Zhou, Zijing Tian, Ye Liu, Zhengzhao Cheng, Kar On Chen, Xibing Hu, Wenbao Wong, Yuk Ming Li, Xiaofen Zhang, Hailin Hu, Ronggui Huang, Pingbo |
author_facet | Cao, Xu Zhou, Zijing Tian, Ye Liu, Zhengzhao Cheng, Kar On Chen, Xibing Hu, Wenbao Wong, Yuk Ming Li, Xiaofen Zhang, Hailin Hu, Ronggui Huang, Pingbo |
author_sort | Cao, Xu |
collection | PubMed |
description | Anoctamin-1 (ANO1) (TMEM16A) is a calcium-activated chloride channel that plays critical roles in diverse physiological processes, such as sensory transduction and epithelial secretion. ANO1 levels have been shown to be altered under physiological and pathological conditions, although the molecular mechanisms that control ANO1 protein levels remain unclear. The ubiquitin–proteasome system is known to regulate the levels of numerous ion channels, but little information is available regarding whether and how ubiquitination regulates levels of ANO1. Here, we showed that two E3 ligases, TRIM23 and TRIM21, physically interact with the C terminus of ANO1. In vitro and in vivo assays demonstrated that whereas TRIM23 ubiquitinated ANO1 leading to its stabilization, TRIM21 ubiquitinated ANO1 and induced its degradation. Notably, ANO1 regulation by TRIM23 and TRIM21 is involved in chemical-induced pain sensation, salivary secretion, and heart-rate control in mice, and TRIM23 also mediates ANO1 upregulation induced by epidermal growth factor treatment. Our results suggest that these two antagonistic E3 ligases act together to control ANO1 expression and function. Our findings reveal a previously unrecognized mechanism for regulating ANO1 protein levels and identify a potential molecular link between ANO1 regulation, epidermal growth factor, and other signaling pathways. |
format | Online Article Text |
id | pubmed-8191318 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-81913182021-06-16 Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels Cao, Xu Zhou, Zijing Tian, Ye Liu, Zhengzhao Cheng, Kar On Chen, Xibing Hu, Wenbao Wong, Yuk Ming Li, Xiaofen Zhang, Hailin Hu, Ronggui Huang, Pingbo J Biol Chem Research Article Anoctamin-1 (ANO1) (TMEM16A) is a calcium-activated chloride channel that plays critical roles in diverse physiological processes, such as sensory transduction and epithelial secretion. ANO1 levels have been shown to be altered under physiological and pathological conditions, although the molecular mechanisms that control ANO1 protein levels remain unclear. The ubiquitin–proteasome system is known to regulate the levels of numerous ion channels, but little information is available regarding whether and how ubiquitination regulates levels of ANO1. Here, we showed that two E3 ligases, TRIM23 and TRIM21, physically interact with the C terminus of ANO1. In vitro and in vivo assays demonstrated that whereas TRIM23 ubiquitinated ANO1 leading to its stabilization, TRIM21 ubiquitinated ANO1 and induced its degradation. Notably, ANO1 regulation by TRIM23 and TRIM21 is involved in chemical-induced pain sensation, salivary secretion, and heart-rate control in mice, and TRIM23 also mediates ANO1 upregulation induced by epidermal growth factor treatment. Our results suggest that these two antagonistic E3 ligases act together to control ANO1 expression and function. Our findings reveal a previously unrecognized mechanism for regulating ANO1 protein levels and identify a potential molecular link between ANO1 regulation, epidermal growth factor, and other signaling pathways. American Society for Biochemistry and Molecular Biology 2021-05-03 /pmc/articles/PMC8191318/ /pubmed/33957127 http://dx.doi.org/10.1016/j.jbc.2021.100738 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Cao, Xu Zhou, Zijing Tian, Ye Liu, Zhengzhao Cheng, Kar On Chen, Xibing Hu, Wenbao Wong, Yuk Ming Li, Xiaofen Zhang, Hailin Hu, Ronggui Huang, Pingbo Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels |
title | Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels |
title_full | Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels |
title_fullStr | Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels |
title_full_unstemmed | Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels |
title_short | Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels |
title_sort | opposing roles of e3 ligases trim23 and trim21 in regulation of ion channel ano1 protein levels |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191318/ https://www.ncbi.nlm.nih.gov/pubmed/33957127 http://dx.doi.org/10.1016/j.jbc.2021.100738 |
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