Morgan, DJ;
Poolman, TM;
Williamson, AJK;
Wang, Z;
Clark, NR;
Ma'ayan, A;
Whetton, AD;
... Ray, DW; + view all
(2016)
Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production.
Scientific Reports
, 6
, Article 26419. 10.1038/srep26419.
Preview |
Text
Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production.pdf - Published Version Download (1MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/srep26419 |
| Publisher version: | http://dx.doi.org/10.1038/srep26419 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | AMINO-ACID, EXPRESSION, LYMPHOMA, GENE, LOCALIZATION, RESISTANCE, INSERTION, GAMMA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10103191 |
Archive Staff Only
 |
View Item |
