TY - JOUR
T1 - Binding of carbonic anhydrase IX to 45S rDNA genes is prevented by exportin-1 in hypoxic cells
AU - Sasso, Emanuele
AU - Vitale, Monica
AU - Monteleone, Francesca
AU - Boffo, Francesca Ludovica
AU - Santoriello, Margherita
AU - Sarnataro, Daniela
AU - Garbi, Corrado
AU - Sabatella, Mariangela
AU - Crifò, Bianca
AU - Paolella, Luca Alfredo
AU - Minopoli, Giuseppina
AU - Winum, Jean Yves
AU - Zambrano, Nicola
N1 - Publisher Copyright:
© 2015 Emanuele Sasso et al.
PY - 2015/2/22
Y1 - 2015/2/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84924529863&partnerID=8YFLogxK
U2 - 10.1155/2015/674920
DO - 10.1155/2015/674920
M3 - Article
C2 - 25793203
AN - SCOPUS:84924529863
SN - 2314-6133
VL - 2015
JO - BioMed Research International
JF - BioMed Research International
M1 - 674920
ER -