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Carbonic anhydrase IX subcellular localization in normoxic and hypoxic SH-SY5Y neuroblastoma cells is assisted by its C-terminal protein interaction domain()

The human carbonic anhydrase IX (CA IX) is a hypoxia-induced transmembrane protein belonging to the α-CA enzyme family. It has a crucial role in pH regulation in hypoxic cells and acts by buffering intracellular acidosis induced by hypoxia. Indeed, it is frequently expressed in cancer cells, where i...

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Autores principales: Succoio, Mariangela, Amiranda, Sara, Sasso, Emanuele, Marciano, Carmen, Finizio, Arianna, De Simone, Giuseppina, Garbi, Corrado, Zambrano, Nicola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432983/
https://www.ncbi.nlm.nih.gov/pubmed/37600419
http://dx.doi.org/10.1016/j.heliyon.2023.e18885
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author Succoio, Mariangela
Amiranda, Sara
Sasso, Emanuele
Marciano, Carmen
Finizio, Arianna
De Simone, Giuseppina
Garbi, Corrado
Zambrano, Nicola
author_facet Succoio, Mariangela
Amiranda, Sara
Sasso, Emanuele
Marciano, Carmen
Finizio, Arianna
De Simone, Giuseppina
Garbi, Corrado
Zambrano, Nicola
author_sort Succoio, Mariangela
collection PubMed
description The human carbonic anhydrase IX (CA IX) is a hypoxia-induced transmembrane protein belonging to the α-CA enzyme family. It has a crucial role in pH regulation in hypoxic cells and acts by buffering intracellular acidosis induced by hypoxia. Indeed, it is frequently expressed in cancer cells, where it contributes to tumor progression. CA IX is also able to localize in the nucleus, where it contributes to 47S rRNA precursor genes transcription; however, the mechanisms assisting its nuclear translocation still remain unclear. The aim of our study was to deepen the understanding of the mechanisms involved in CA IX subcellular distribution. To this purpose, we implemented a site-directed mutagenesis approach targeting the C-terminal domain of CA IX and evaluated the subcellular distribution of the wild-type and mutant proteins in the SH-SY5Y cell line. The mutant proteins showed impaired binding ability and altered subcellular distribution in both normoxic and hypoxic conditions. Our data suggest that CA IX nuclear translocation depends on its transit through the secretory and the endocytic pathways.
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spelling pubmed-104329832023-08-18 Carbonic anhydrase IX subcellular localization in normoxic and hypoxic SH-SY5Y neuroblastoma cells is assisted by its C-terminal protein interaction domain() Succoio, Mariangela Amiranda, Sara Sasso, Emanuele Marciano, Carmen Finizio, Arianna De Simone, Giuseppina Garbi, Corrado Zambrano, Nicola Heliyon Research Article The human carbonic anhydrase IX (CA IX) is a hypoxia-induced transmembrane protein belonging to the α-CA enzyme family. It has a crucial role in pH regulation in hypoxic cells and acts by buffering intracellular acidosis induced by hypoxia. Indeed, it is frequently expressed in cancer cells, where it contributes to tumor progression. CA IX is also able to localize in the nucleus, where it contributes to 47S rRNA precursor genes transcription; however, the mechanisms assisting its nuclear translocation still remain unclear. The aim of our study was to deepen the understanding of the mechanisms involved in CA IX subcellular distribution. To this purpose, we implemented a site-directed mutagenesis approach targeting the C-terminal domain of CA IX and evaluated the subcellular distribution of the wild-type and mutant proteins in the SH-SY5Y cell line. The mutant proteins showed impaired binding ability and altered subcellular distribution in both normoxic and hypoxic conditions. Our data suggest that CA IX nuclear translocation depends on its transit through the secretory and the endocytic pathways. Elsevier 2023-08-02 /pmc/articles/PMC10432983/ /pubmed/37600419 http://dx.doi.org/10.1016/j.heliyon.2023.e18885 Text en © 2023 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
Succoio, Mariangela
Amiranda, Sara
Sasso, Emanuele
Marciano, Carmen
Finizio, Arianna
De Simone, Giuseppina
Garbi, Corrado
Zambrano, Nicola
Carbonic anhydrase IX subcellular localization in normoxic and hypoxic SH-SY5Y neuroblastoma cells is assisted by its C-terminal protein interaction domain()
title Carbonic anhydrase IX subcellular localization in normoxic and hypoxic SH-SY5Y neuroblastoma cells is assisted by its C-terminal protein interaction domain()
title_full Carbonic anhydrase IX subcellular localization in normoxic and hypoxic SH-SY5Y neuroblastoma cells is assisted by its C-terminal protein interaction domain()
title_fullStr Carbonic anhydrase IX subcellular localization in normoxic and hypoxic SH-SY5Y neuroblastoma cells is assisted by its C-terminal protein interaction domain()
title_full_unstemmed Carbonic anhydrase IX subcellular localization in normoxic and hypoxic SH-SY5Y neuroblastoma cells is assisted by its C-terminal protein interaction domain()
title_short Carbonic anhydrase IX subcellular localization in normoxic and hypoxic SH-SY5Y neuroblastoma cells is assisted by its C-terminal protein interaction domain()
title_sort carbonic anhydrase ix subcellular localization in normoxic and hypoxic sh-sy5y neuroblastoma cells is assisted by its c-terminal protein interaction domain()
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432983/
https://www.ncbi.nlm.nih.gov/pubmed/37600419
http://dx.doi.org/10.1016/j.heliyon.2023.e18885
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