title: F-box only protein 9 is an E3 ubiquitin ligase of PPARγ.
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.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Marine Biotechnology Research Center, Korea Institute of Ocean Science & Technology, Ansan, Korea.
authors.forename: Kyeong Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Soo Heon
authors.initials: SH
authors.lastname: Kwak
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young Do
authors.initials: YD
authors.lastname: Koo
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
authors.forename: Yun-Kyung
authors.initials: YK
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hak Mo
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D044783:F-Box Proteins / Q000378:metabolism*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D060066:Protein Interaction Maps; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D044783:F-Box Proteins; C582681:FBXO9 protein, mouse; D047495:PPAR gamma; D044767:Ubiquitin-Protein Ligases