F-box only protein 9 is an E3 ubiquitin ligase of PPAR?.

ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPAR?) is a critical regulator of carbohydrate and lipid metabolism, adipocyte differentiation and inflammatory response. Post-translational modification of PPAR? and its degradation involve several pathways, including the ubiquitin-proteasome system. Here, we identified F-box only protein 9 (FBXO9) as an E3 ubiquitin ligase of PPAR?. We screened interacting partners of PPAR? using immunoprecipitation and mass spectrometric analysis and identified FBXO9 as an E3 ubiquitin ligase of PPAR?. FBXO9 directly interacted with PPAR? through the activation function-1 domain and ligand-binding domain. FBXO9 decreased the protein stability of PPAR? through induction of ubiquitination. We found that the F-box motif of FBXO9 was required for its ubiquitination function. The activity of PPAR? was significantly decreased by FBXO9 overexpression. Furthermore, FBXO9 overexpression in 3T3-L1 adipocytes resulted in decreased levels of endogenous PPAR? and suppression of adipogenesis. These results suggest that FBXO9 is an important enzyme that regulates the stability and activity of PPAR? through ubiquitination.

SUBMITTER: Lee KW 

PROVIDER: S-EPMC4910150 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature