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Suh, Pann-Ghill
BioSignal Network Lab (BSN)
Research Interests
  • Signal transduction, cancer, metabolism, phospholipase C

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Flightless-1, a novel transcriptional modulator of PPARγ through competing with RXRα

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Title
Flightless-1, a novel transcriptional modulator of PPARγ through competing with RXRα
Author
Choi, Jin SilChoi, Sun-SilKim, Eun SunSeo, Young KyoSeo, Jeong KonKim, Eung-KyuSuh, Pann-GhillChoi, Jang Hyun
Issue Date
2015-03
Publisher
ELSEVIER SCIENCE INC
Citation
CELLULAR SIGNALLING, v.27, no.3, pp.614 - 620
Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor family and plays key roles in glucose and lipid metabolism. Its transcriptional control of target genes is mediated by ligand-dependent recruitment of coactivators. In this study, we demonstrate that a novel transcriptional modulator of PPARγ, Flightless-I (FLII) binds directly to and suppresses the transcriptional activity of PPARγ. The LXXLL motif within the leucine-rich repeat (LRR) domain of FLII interacts directly with the DNA-binding domain of PPARγ. Interestingly, in the presence of PPARγ ligands, such as rosiglitazone and SR1664, this interaction was abolished in vitro. When FLII was overexpressed, both the transcriptional activity of PPARγ and adipogenesis were suppressed significantly, whereas specific knockdown of FLII reversed these effects. Furthermore, DNA occupancy of PPARγ on its target gene promoters was enhanced by FLII knockdown, and the interaction between PPARγ and retinoid X receptor α (RXRα) was blocked by FLII. Together, these findings strongly suggest that FLII functions in PPARγ activation as a molecular switch to repress transcriptional activity by interrupting formation of the PPARγ/RXRα complex, and FLII may serve as a novel therapeutic target in the treatment of adiposity-related metabolic syndromes.
URI
https://scholarworks.unist.ac.kr/handle/201301/10049
URL
http://www.sciencedirect.com/science/article/pii/S0898656814003891
DOI
10.1016/j.cellsig.2014.11.035
ISSN
0898-6568
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BIO_Journal Papers
SE_Journal Papers
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