Flightless-1, a novel transcriptional modulator of PPARγ through competing with RXRα
| Autor: | Pann-Ghill Suh, Eun Sun Kim, Young-Kyo Seo, Jeong Kon Seo, Jang Hyun Choi, Sun-Sil Choi, Eung-Kyun Kim, Jin Sil Choi |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Transcription
Genetic Amino Acid Motifs Biology Retinoid X receptor Rosiglitazone Mice 3T3-L1 Cells Transcriptional regulation Animals Humans RNA Small Interfering Promoter Regions Genetic Receptor Gene knockdown Adipogenesis Retinoid X Receptor alpha Microfilament Proteins Promoter Lipid metabolism Cell Biology Molecular biology Recombinant Proteins Cell biology PPAR gamma Cytoskeletal Proteins HEK293 Cells Nuclear receptor Trans-Activators RNA Interference Thiazolidinediones Carrier Proteins Dimerization Protein Binding |
| Zdroj: | Cellular Signalling. 27:614-620 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/j.cellsig.2014.11.035 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect