Imperial College London
Alternate

ProfessorSimakAli

Faculty of Medicine, Department of Surgery & Cancer

Professor of Molecular Endocrine Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2811simak.ali

 
 
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Location

 

133ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Fulton:2017:10.1038/cddis.2017.98,
author = {Fulton, J and Mazumder, B and Whitchurch, JB and Monteiro, CJ and Collins, HM and Chan, CM and Clemente, MP and Hernandez-Quiles, M and Stewart, EA and Amoaku, WM and Moran, PM and Mongan, NP and Persson, JL and Ali, S and Heery, DM},
doi = {10.1038/cddis.2017.98},
journal = {Cell Death and Disease},
title = {Heterodimers of photoreceptor-specific nuclear receptor (PNR/NR2E3) and peroxisome proliferator-activated receptor-gamma (PPAR gamma) are disrupted by retinal disease-associated mutations},
url = {http://dx.doi.org/10.1038/cddis.2017.98},
volume = {8},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Photoreceptor-specific nuclear receptor (PNR/NR2E3) and Tailless homolog (TLX/NR2E1) are human orthologs of the NR2E group,a subgroup of phylogenetically related members of the nuclear receptor (NR) superfamily of transcription factors. We assessed theability of these NRs to form heterodimers with other members of the human NRs representing all major subgroups. The TLXligand-binding domain (LBD) did not appear to form homodimers or interact directly with any other NR tested. The PNR LBD wasable to form homodimers, but also exhibited robust interactions with the LBDs of peroxisome proliferator-activated receptor-γ(PPARγ)/NR1C3 and thyroid hormone receptor b (TRb) TRβ/NR1A2. The binding of PNR to PPARγ was specific for this paralog, asno interaction was observed with the LBDs of PPARα/NR1C1 or PPARδ/NR1C2. In support of these findings, PPARγ and PNR werefound to be co-expressed in human retinal tissue extracts and could be co-immunoprecipitated as a native complex. Selectedsequence variants in the PNR LBD associated with human retinopathies, or a mutation in the dimerization region of PPARγ LBDassociated with familial partial lipodystrophy type 3, were found to disrupt PNR/PPARγ complex formation. Wild-type PNR, but nota PNR309G mutant, was able to repress PPARγ-mediated transcription in reporter assays. In summary, our results reveal novelheterodimer interactions in the NR superfamily, suggesting previously unknown functional interactions of PNR with PPARγ andTRβ that have potential importance in retinal development and disease.
AU  - Fulton,J
AU  - Mazumder,B
AU  - Whitchurch,JB
AU  - Monteiro,CJ
AU  - Collins,HM
AU  - Chan,CM
AU  - Clemente,MP
AU  - Hernandez-Quiles,M
AU  - Stewart,EA
AU  - Amoaku,WM
AU  - Moran,PM
AU  - Mongan,NP
AU  - Persson,JL
AU  - Ali,S
AU  - Heery,DM
DO  - 10.1038/cddis.2017.98
PY  - 2017///
SN  - 2041-4889
TI  - Heterodimers of photoreceptor-specific nuclear receptor (PNR/NR2E3) and peroxisome proliferator-activated receptor-gamma (PPAR gamma) are disrupted by retinal disease-associated mutations
T2  - Cell Death and Disease
UR  - http://dx.doi.org/10.1038/cddis.2017.98
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000397447100042&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/49211
VL  - 8
ER  -
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