Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production.
Sci Rep
; 6: 26419, 2016 05 26.
Article
em En
| MEDLINE
| ID: mdl-27226058
ABSTRACT
The glucocorticoid receptor (GR), a nuclear receptor and major drug target, has a highly conserved minor splice variant, GRγ, which differs by a single arginine within the DNA binding domain. GRγ, which comprises 10% of all GR transcripts, is constitutively expressed and tightly conserved through mammalian evolution, suggesting an important non-redundant role. However, to date no specific role for GRγ has been reported. We discovered significant differences in subcellular localisation, and nuclear-cytoplasmic shuttling in response to ligand. In addition the GRγ transcriptome and protein interactome was distinct, and with a gene ontology signal for mitochondrial regulation which was confirmed using Seahorse technology. We propose that evolutionary conservation of the single additional arginine in GRγ is driven by a distinct, non-redundant functional profile, including regulation of mitochondrial function.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Glucocorticoides
/
Trifosfato de Adenosina
/
Mitocôndrias
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article