KMID : 0620920160480050005
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Experimental & Molecular Medicine 2016 Volume.48 No. 5 p.5 ~ p.5
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F-box only protein 9 is an E3 ubiquitin ligase of PPAR¥ã
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Lee Kyeong-Won
Kwak Soo-Heon Koo Young-Do Cho Yun-Kyung Lee Hak-Mo Jung Hye-Seung Cho Young-Min Park Young-Joo Chung Sung-Soo Park Kyong-Soo
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Abstract
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Peroxisome proliferator-activated receptor gamma (PPAR¥ã) is a critical regulator of carbohydrate and lipid metabolism, adipocyte differentiation and inflammatory response. Post-translational modification of PPAR¥ã 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¥ã. We screened interacting partners of PPAR¥ã using immunoprecipitation and mass spectrometric analysis and identified FBXO9 as an E3 ubiquitin ligase of PPAR¥ã. FBXO9 directly interacted with PPAR¥ã through the activation function-1 domain and ligand-binding domain. FBXO9 decreased the protein stability of PPAR¥ã through induction of ubiquitination. We found that the F-box motif of FBXO9 was required for its ubiquitination function. The activity of PPAR¥ã was significantly decreased by FBXO9 overexpression. Furthermore, FBXO9 overexpression in 3T3-L1 adipocytes resulted in decreased levels of endogenous PPAR¥ã and suppression of adipogenesis. These results suggest that FBXO9 is an important enzyme that regulates the stability and activity of PPAR¥ã through ubiquitination.
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KEYWORD
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