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Alternatively Spliced Isoforms of K(V)10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes
K(V)10.1 is a voltage-gated potassium channel expressed selectively in the mammalian brain but also aberrantly in cancer cells. In this study we identified short splice variants of K(V)10.1 resulting from exon-skipping events (E65 and E70) in human brain and cancer cell lines. The presence of the va...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683259/ https://www.ncbi.nlm.nih.gov/pubmed/26518875 http://dx.doi.org/10.1074/jbc.M115.668749 |
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author | Ramos Gomes, Fernanda Romaniello, Vincenzo Sánchez, Araceli Weber, Claudia Narayanan, Pratibha Psol, Maryna Pardo, Luis A. |
author_facet | Ramos Gomes, Fernanda Romaniello, Vincenzo Sánchez, Araceli Weber, Claudia Narayanan, Pratibha Psol, Maryna Pardo, Luis A. |
author_sort | Ramos Gomes, Fernanda |
collection | PubMed |
description | K(V)10.1 is a voltage-gated potassium channel expressed selectively in the mammalian brain but also aberrantly in cancer cells. In this study we identified short splice variants of K(V)10.1 resulting from exon-skipping events (E65 and E70) in human brain and cancer cell lines. The presence of the variants was confirmed by Northern blot and RNase protection assays. Both variants completely lacked the transmembrane domains of the channel and produced cytoplasmic proteins without channel function. In a reconstituted system, both variants co-precipitated with the full-length channel and induced a robust down-regulation of K(V)10.1 current when co-expressed with the full-length form, but their effect was mechanistically different. E65 required a tetramerization domain and induced a reduction in the overall expression of full-length K(V)10.1, whereas E70 mainly affected its glycosylation pattern. E65 triggered the activation of cyclin-dependent kinases in Xenopus laevis oocytes, suggesting a role in cell cycle control. Our observations highlight the relevance of noncanonical functions for the oncogenicity of K(V)10.1, which need to be considered when ion channels are targeted for cancer therapy. |
format | Online Article Text |
id | pubmed-4683259 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-46832592015-12-21 Alternatively Spliced Isoforms of K(V)10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes Ramos Gomes, Fernanda Romaniello, Vincenzo Sánchez, Araceli Weber, Claudia Narayanan, Pratibha Psol, Maryna Pardo, Luis A. J Biol Chem Cell Biology K(V)10.1 is a voltage-gated potassium channel expressed selectively in the mammalian brain but also aberrantly in cancer cells. In this study we identified short splice variants of K(V)10.1 resulting from exon-skipping events (E65 and E70) in human brain and cancer cell lines. The presence of the variants was confirmed by Northern blot and RNase protection assays. Both variants completely lacked the transmembrane domains of the channel and produced cytoplasmic proteins without channel function. In a reconstituted system, both variants co-precipitated with the full-length channel and induced a robust down-regulation of K(V)10.1 current when co-expressed with the full-length form, but their effect was mechanistically different. E65 required a tetramerization domain and induced a reduction in the overall expression of full-length K(V)10.1, whereas E70 mainly affected its glycosylation pattern. E65 triggered the activation of cyclin-dependent kinases in Xenopus laevis oocytes, suggesting a role in cell cycle control. Our observations highlight the relevance of noncanonical functions for the oncogenicity of K(V)10.1, which need to be considered when ion channels are targeted for cancer therapy. American Society for Biochemistry and Molecular Biology 2015-12-18 2015-10-30 /pmc/articles/PMC4683259/ /pubmed/26518875 http://dx.doi.org/10.1074/jbc.M115.668749 Text en © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) . |
spellingShingle | Cell Biology Ramos Gomes, Fernanda Romaniello, Vincenzo Sánchez, Araceli Weber, Claudia Narayanan, Pratibha Psol, Maryna Pardo, Luis A. Alternatively Spliced Isoforms of K(V)10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes |
title | Alternatively Spliced Isoforms of K(V)10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes |
title_full | Alternatively Spliced Isoforms of K(V)10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes |
title_fullStr | Alternatively Spliced Isoforms of K(V)10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes |
title_full_unstemmed | Alternatively Spliced Isoforms of K(V)10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes |
title_short | Alternatively Spliced Isoforms of K(V)10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes |
title_sort | alternatively spliced isoforms of k(v)10.1 potassium channels modulate channel properties and can activate cyclin-dependent kinase in xenopus oocytes |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683259/ https://www.ncbi.nlm.nih.gov/pubmed/26518875 http://dx.doi.org/10.1074/jbc.M115.668749 |
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