F-box only protein 9 is an E3 ubiquitin ligase of PPARγ.
- Author:
Kyeong Won LEE
1
;
Soo Heon KWAK
;
Young Do KOO
;
Yun Kyung CHO
;
Hak Mo LEE
;
Hye Seung JUNG
;
Young Min CHO
;
Young Joo PARK
;
Sung Soo CHUNG
;
Kyong Soo PARK
Author Information
- Publication Type:Original Article
- MeSH: Adipocytes; Adipogenesis; F-Box Motifs; Immunoprecipitation; Lipid Metabolism; PPAR gamma; Protein Processing, Post-Translational; Protein Stability; Ubiquitin; Ubiquitin-Protein Ligases*; Ubiquitination
- From:Experimental & Molecular Medicine 2016;48(5):e234-
- CountryRepublic of Korea
- Language:English
- Abstract: Peroxisome proliferator-activated receptor gamma (PPARγ) is a critical regulator of carbohydrate and lipid metabolism, adipocyte differentiation and inflammatory response. Post-translational modification of PPARγ 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 PPARγ. We screened interacting partners of PPARγ using immunoprecipitation and mass spectrometric analysis and identified FBXO9 as an E3 ubiquitin ligase of PPARγ. FBXO9 directly interacted with PPARγ through the activation function-1 domain and ligand-binding domain. FBXO9 decreased the protein stability of PPARγ through induction of ubiquitination. We found that the F-box motif of FBXO9 was required for its ubiquitination function. The activity of PPARγ was significantly decreased by FBXO9 overexpression. Furthermore, FBXO9 overexpression in 3T3-L1 adipocytes resulted in decreased levels of endogenous PPARγ and suppression of adipogenesis. These results suggest that FBXO9 is an important enzyme that regulates the stability and activity of PPARγ through ubiquitination.
