title: Binding of carbonic anhydrase IX to 45S rDNA genes is prevented by exportin-1 in hypoxic cells.
abstract: 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 45 S 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 45 S 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. 45 S 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 45 S rDNA gene promoters.
authors: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, Italy ; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy ; Associazione Culturale DiSciMuS RFC, 80026 Casoria, Italy.
authors: Emanuele
authors: E
authors: Sasso
authors: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, Italy ; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
authors: Monica
authors: M
authors: Vitale
authors: CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy ; Associazione Culturale DiSciMuS RFC, 80026 Casoria, Italy.
authors: Francesca
authors: F
authors: Monteleone
authors: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, Italy ; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
authors: Francesca Ludovica
authors: FL
authors: Boffo
authors: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, Italy.
authors: Margherita
authors: M
authors: Santoriello
authors: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, Italy ; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
authors: Daniela
authors: 0000-0002-6094-8384
authors: D
authors: Sarnataro
authors: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, Italy.
authors: Corrado
authors: C
authors: Garbi
authors: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, Italy ; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
authors: Mariangela
authors: 0000-0002-9177-4946
authors: M
authors: Sabatella
authors: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, Italy ; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
authors: Bianca
authors: B
authors: Crifò
authors: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, Italy ; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
authors: Luca Alfredo
authors: LA
authors: Paolella
authors: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, Italy ; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy.
authors: Giuseppina
authors: 0000-0001-5537-8156
authors: G
authors: Minopoli
authors: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, Université Montpellier I & II, ENSCM, 34296 Montpellier, France.
authors: Jean-Yves
authors: JY
authors: Winum
authors: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, 80131 Napoli, Italy ; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy ; Associazione Culturale DiSciMuS RFC, 80026 Casoria, Italy.
authors: Nicola
authors: N
authors: Zambrano
mesh_terms: D000138:Acidosis / Q000235:genetics / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D000097606:Exportin 1 Protein
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D002843:Chromatin; D004275:DNA, Ribosomal; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C089226:CA9 protein, human