Binding of Carbonic Anhydrase IX to 45S rDNA Genes Is Prevented by Exportin-1 in Hypoxic Cells

Carbonic anhydrase IX (CA IX) is a surrogate marker of hypoxia, involved in survival and pH regulation in hypoxic cells. We have recently characterized its interactome, describing a set of proteins interacting with CA IX, mainly in hypoxic cells, including several members of the nucleocytoplasmic sh...

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Main Authors: Emanuele Sasso, Monica Vitale, Francesca Monteleone, Francesca Ludovica Boffo, Margherita Santoriello, Daniela Sarnataro, Corrado Garbi, Mariangela Sabatella, Bianca Crifò, Luca Alfredo Paolella, Giuseppina Minopoli, Jean-Yves Winum, Nicola Zambrano
Format: Article
Language:English
Published: Hindawi Limited 2015-01-01
Series:BioMed Research International
Online Access:http://dx.doi.org/10.1155/2015/674920
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spelling doaj-96d8f0a204eb43c9b239f525e304cd5b2020-11-25T01:07:31ZengHindawi LimitedBioMed Research International2314-61332314-61412015-01-01201510.1155/2015/674920674920Binding of Carbonic Anhydrase IX to 45S rDNA Genes Is Prevented by Exportin-1 in Hypoxic CellsEmanuele Sasso0Monica Vitale1Francesca Monteleone2Francesca Ludovica Boffo3Margherita Santoriello4Daniela Sarnataro5Corrado Garbi6Mariangela Sabatella7Bianca Crifò8Luca Alfredo Paolella9Giuseppina Minopoli10Jean-Yves Winum11Nicola Zambrano12Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, ItalyCEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, ItalyInstitut des Biomolécules Max Mousseron, UMR 5247 CNRS, Université Montpellier I & II, ENSCM, 34296 Montpellier, FranceDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, ItalyCarbonic anhydrase IX (CA IX) is a surrogate marker of hypoxia, involved in survival and pH regulation in hypoxic cells. We have recently characterized its interactome, describing a set of proteins interacting with CA IX, mainly in hypoxic cells, including several members of the nucleocytoplasmic shuttling apparatuses. Accordingly, we described complex subcellular localization for this enzyme in human cells, as well as the redistribution of a carbonic anhydrase IX pool to nucleoli during hypoxia. Starting from this evidence, we analyzed the possible contribution of carbonic anhydrase IX to transcription of the 45S rDNA genes, a process occurring in nucleoli. We highlighted the binding of carbonic anhydrase IX to nucleolar chromatin, which is regulated by oxygen levels. In fact, CA IX was found on 45S rDNA gene promoters in normoxic cells and less represented on these sites, in hypoxic cells and in cells subjected to acetazolamide-induced acidosis. Both conditions were associated with increased representation of carbonic anhydrase IX/exportin-1 complexes in nucleoli. 45S rRNA transcript levels were accordingly downrepresented. Inhibition of nuclear export by leptomycin B suggests a model in which exportin-1 acts as a decoy, in hypoxic cells, preventing carbonic anhydrase IX association with 45S rDNA gene promoters.http://dx.doi.org/10.1155/2015/674920
collection DOAJ
language English
format Article
sources DOAJ
author Emanuele Sasso
Monica Vitale
Francesca Monteleone
Francesca Ludovica Boffo
Margherita Santoriello
Daniela Sarnataro
Corrado Garbi
Mariangela Sabatella
Bianca Crifò
Luca Alfredo Paolella
Giuseppina Minopoli
Jean-Yves Winum
Nicola Zambrano
spellingShingle Emanuele Sasso
Monica Vitale
Francesca Monteleone
Francesca Ludovica Boffo
Margherita Santoriello
Daniela Sarnataro
Corrado Garbi
Mariangela Sabatella
Bianca Crifò
Luca Alfredo Paolella
Giuseppina Minopoli
Jean-Yves Winum
Nicola Zambrano
Binding of Carbonic Anhydrase IX to 45S rDNA Genes Is Prevented by Exportin-1 in Hypoxic Cells
BioMed Research International
author_facet Emanuele Sasso
Monica Vitale
Francesca Monteleone
Francesca Ludovica Boffo
Margherita Santoriello
Daniela Sarnataro
Corrado Garbi
Mariangela Sabatella
Bianca Crifò
Luca Alfredo Paolella
Giuseppina Minopoli
Jean-Yves Winum
Nicola Zambrano
author_sort Emanuele Sasso
title Binding of Carbonic Anhydrase IX to 45S rDNA Genes Is Prevented by Exportin-1 in Hypoxic Cells
title_short Binding of Carbonic Anhydrase IX to 45S rDNA Genes Is Prevented by Exportin-1 in Hypoxic Cells
title_full Binding of Carbonic Anhydrase IX to 45S rDNA Genes Is Prevented by Exportin-1 in Hypoxic Cells
title_fullStr Binding of Carbonic Anhydrase IX to 45S rDNA Genes Is Prevented by Exportin-1 in Hypoxic Cells
title_full_unstemmed Binding of Carbonic Anhydrase IX to 45S rDNA Genes Is Prevented by Exportin-1 in Hypoxic Cells
title_sort binding of carbonic anhydrase ix to 45s rdna genes is prevented by exportin-1 in hypoxic cells
publisher Hindawi Limited
series BioMed Research International
issn 2314-6133
2314-6141
publishDate 2015-01-01
description Carbonic anhydrase IX (CA IX) is a surrogate marker of hypoxia, involved in survival and pH regulation in hypoxic cells. We have recently characterized its interactome, describing a set of proteins interacting with CA IX, mainly in hypoxic cells, including several members of the nucleocytoplasmic shuttling apparatuses. Accordingly, we described complex subcellular localization for this enzyme in human cells, as well as the redistribution of a carbonic anhydrase IX pool to nucleoli during hypoxia. Starting from this evidence, we analyzed the possible contribution of carbonic anhydrase IX to transcription of the 45S rDNA genes, a process occurring in nucleoli. We highlighted the binding of carbonic anhydrase IX to nucleolar chromatin, which is regulated by oxygen levels. In fact, CA IX was found on 45S rDNA gene promoters in normoxic cells and less represented on these sites, in hypoxic cells and in cells subjected to acetazolamide-induced acidosis. Both conditions were associated with increased representation of carbonic anhydrase IX/exportin-1 complexes in nucleoli. 45S rRNA transcript levels were accordingly downrepresented. Inhibition of nuclear export by leptomycin B suggests a model in which exportin-1 acts as a decoy, in hypoxic cells, preventing carbonic anhydrase IX association with 45S rDNA gene promoters.
url http://dx.doi.org/10.1155/2015/674920
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