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Sci Rep. 2016 May 26;6:26419. doi: 10.1038/srep26419.

Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production.

Author information

1
School of Computer Sciences, University of Manchester, Kilburn Building, Oxford Road, Manchester, Uk, M13 9PL.
2
Faculty of Medical and Human Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, UK, M13 9PT.
3
Manchester Centre for Nuclear Hormone Research in Disease, University of Manchester, AV Hill Building, Oxford Road, Manchester, UK, M13 9PT.
4
Manchester Academic Health Sciences Centre, University of Manchester, AV Hill Building, Oxford Road, Manchester, UK, M13 9PT.
5
Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA.
6
Stoller Biomarker Discovery Centre, University of Manchester, Wolfson Molecular Imaging Centre, Palatine Road, Manchester, UK, M20 3LJ.
7
Faculty of Life Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, UK, M13 9PT.
8
Faculty of Medicine and Health, University of Leeds, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, UK, LS9 7TF.

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.

PMID:
27226058
PMCID:
PMC4881047
DOI:
10.1038/srep26419
[Indexed for MEDLINE]
Free PMC Article

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