title: Control of adipogenesis by the SUMO-specific protease SENP2.
abstract: Here, we demonstrate that SENP2, a desumoylating enzyme, plays a critical role in the control of adipogenesis. SENP2 expression was markedly increased upon the induction of adipocyte differentiation, and this increase was dependent on protein kinase A activation. Remarkably, knockdown of SENP2 led to a dramatic attenuation of adipogenesis with a marked decrease in PPARgamma and C/EBPalpha mRNA levels. Knockdown of SENP2 also caused a marked reduction in the level of C/EBPbeta protein but not in that of C/EBPbeta mRNA. Interestingly, sumoylation of C/EBPbeta dramatically increased its ubiquitination and destabilization, and this increase could be reversed by SENP2. In addition, overexpression of C/EBPbeta could overcome the inhibitory effect of SENP2 knockdown on adipogenesis. Furthermore, SENP2 was absolutely required for adipogenesis of preadipocytes implanted into mice. These results establish a critical role for SENP2 in the regulation of adipogenesis by desumoylation and stabilization of C/EBPbeta and in turn by promoting the expression of its downstream effectors, such as PPARgamma and C/EBPalpha.
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and Department of Internal Medicine, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-744, South Korea.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Chung
authors.forename: Byung Yong
authors.initials: BY
authors.lastname: Ahn
authors.forename: Min
authors.initials: M
authors.lastname: Kim
authors.forename: Hye Hun
authors.initials: HH
authors.lastname: Choi
authors.forename: Ho Seon
authors.initials: HS
authors.lastname: Park
authors.forename: Shinae
authors.initials: S
authors.lastname: Kang
authors.forename: Sang Gyu
authors.initials: SG
authors.lastname: Park
authors.forename: Young-Bum
authors.initials: YB
authors.lastname: Kim
authors.forename: Young Min
authors.initials: YM
authors.lastname: Cho
authors.forename: Hong Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Chin Ha
authors.initials: CH
authors.lastname: Chung
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000201:enzymology; D050156:Adipogenesis; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003546:Cysteine Endopeptidases; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D051379:Mice; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D055550:Protein Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D054875:Ubiquitination
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D009097:Multienzyme Complexes; D047495:PPAR gamma; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025841:Small Ubiquitin-Related Modifier Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; C439066:Senp2 protein, mouse