Control of adipogenesis by the SUMO-specific protease SENP2.
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.
Chung
Sung Soo
SS
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.
Ahn
Byung Yong
BY
Kim
Min
M
Choi
Hye Hun
HH
Park
Ho Seon
HS
Kang
Shinae
S
Park
Sang Gyu
SG
Kim
Young-Bum
YB
Cho
Young Min
YM
Lee
Hong Kyu
HK
Chung
Chin Ha
CH
Park
Kyong Soo
KS
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
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