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SUMO-C/EBPbeta + H2O
SUMO + C/EBPbeta
SUMO-Pc2/CBX4 conjugate + H2O
SUMO + Pc2/CBX4
SUMOylated Mdm2 + H2O
?
Mdm2 controls p53 activities critical for G-S transition of mitotic division and endoreduplication in trophoblast proliferation and differentiation
-
-
?
SUMOylated Setdb1 + H2O
?
i.e. SET domain bifurcated 1, a histone methyltransferase for H3K9 trimethylation
-
-
?
(SUMO-1)-Mdm2 conjugate + H2O
SUMO + Mdm2
SUMO-Mdm2 conjugate + H2O
SUMO + Mdm2
SUMOylated myocyte-specific enhancer factor-2A + H2O
deSUMOylated myocyte-specific enhancer factor-2A + SUMO
-
deSUMOylation by enzyme SENP2
-
-
?
SUMO-C/EBPbeta + H2O
SUMO + C/EBPbeta
-
-
-
?
SUMO-C/EBPbeta + H2O
SUMO + C/EBPbeta
sumoylation causes destabilization of the C/EBPbeta protein and that this process can be reversed by SENP2
-
-
?
SUMO-Pc2/CBX4 conjugate + H2O
SUMO + Pc2/CBX4
Pc2/CBX4 is a polycomb repressive complex 1 (PRC1) subunit. SENP2 specifically controls Pc2/CBX4 contained PRC1 activity through regulation of the SUMOylation status of Pc2/CBX4, which facilitates its binding to H3K27me3 in mammalian cells to mediate transcriptional repression
-
-
?
SUMO-Pc2/CBX4 conjugate + H2O
SUMO + Pc2/CBX4
Pc2/CBX4 is a polycomb repressive complex 1 (PRC1) subunit
-
-
?
(SUMO-1)-Mdm2 conjugate + H2O
SUMO + Mdm2
-
-
-
-
?
(SUMO-1)-Mdm2 conjugate + H2O
SUMO + Mdm2
-
SUMO conjugation of Mdm2 induces its co-localization and association with SENP2 at the PML bodies. SENP2 catalyzes the desumoylation process of Mdm2. SENP2 mediated regulation of Mdm2 critical for genome integrity in p53-dependent stress responses
-
-
?
SUMO-Mdm2 conjugate + H2O
SUMO + Mdm2
-
Mdm2 is an important negative regulator of the p53 tumor suppressor. The SENP2 mediated SUMO modification of Mdm2 appears to be crucial for its subcellular trafficking
-
-
?
SUMO-Mdm2 conjugate + H2O
SUMO + Mdm2
-
Mdm2 is an important negative regulator of the p53 tumor suppressor
-
-
?
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SUMO-C/EBPbeta + H2O
SUMO + C/EBPbeta
sumoylation causes destabilization of the C/EBPbeta protein and that this process can be reversed by SENP2
-
-
?
SUMO-Pc2/CBX4 conjugate + H2O
SUMO + Pc2/CBX4
Pc2/CBX4 is a polycomb repressive complex 1 (PRC1) subunit. SENP2 specifically controls Pc2/CBX4 contained PRC1 activity through regulation of the SUMOylation status of Pc2/CBX4, which facilitates its binding to H3K27me3 in mammalian cells to mediate transcriptional repression
-
-
?
(SUMO-1)-Mdm2 conjugate + H2O
SUMO + Mdm2
-
SUMO conjugation of Mdm2 induces its co-localization and association with SENP2 at the PML bodies. SENP2 catalyzes the desumoylation process of Mdm2. SENP2 mediated regulation of Mdm2 critical for genome integrity in p53-dependent stress responses
-
-
?
SUMO-Mdm2 conjugate + H2O
SUMO + Mdm2
-
Mdm2 is an important negative regulator of the p53 tumor suppressor. The SENP2 mediated SUMO modification of Mdm2 appears to be crucial for its subcellular trafficking
-
-
?
SUMOylated myocyte-specific enhancer factor-2A + H2O
deSUMOylated myocyte-specific enhancer factor-2A + SUMO
-
deSUMOylation by enzyme SENP2
-
-
?
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additional information
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Correlation of Senp2 and myostatin expression in cachexia
malfunction
in SENP2 null embryo, SUMOylated Pc2/CBX4 accumulates and Pc2/CBX4 occupancy on the promoters of PcG target genes is markedly increased, leading to repression of Gata4 and Gata6 transcription
malfunction
knockdown of SENP2 leads to a strong attenuation of adipogenesis with a marked decrease in PPARgamma and C/EBPalpha mRNA levels. Knockdown of SENP2 also causes a marked reduction in the level of C/EBPbeta protein but not in that of C/EBPbeta mRNA
physiological function
SENP2 plays a critical role in the control 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
physiological function
SUMO-specific protease 2 is essential for suppression of polycomb group protein-mediated gene silencing during embryonic development. SENP2 specifically controls Pc2/CBX4 contained PRC1 activity through regulation of the SUMOylation status of Pc2/CBX4, which facilitates its binding to H3K27me3 in mammalian cells to mediate transcriptional repression
physiological function
adipocyte Senp2 deficiency results in less adipose lipid storage accompanied by an ectopic fat accumulation and insulin resistance under high-fat diet feeding. SET domain bifurcated 1 (Setdb1) is a SUMOylated protein and SUMOylation promotes Setdb1 occupancy on the promoter locus of Pparg and Cebpa genes to suppress their expressions via histone H3K9me3. Senp2 can suppress Setdb1 function by deSUMOylation. In adipocyte Senp2-deficiency mice, accumulation of the SUMOylated Setdb1 suppresses the expression of Pparg and Cebpa genes as well as lipid metabolism-related target genes
physiological function
development of a mouse strain permitting conditional inactivation of SENP2. Mice homozygous for germline deletion of the conditional allele exhibit trophoblast defects and embryonic abnormalities resembling the global SENP2 knockout. SENP2 is dispensable in embryogenesis. Placental expression of SENP2 is necessary and sufficient for embryonic heart and brain development. SENP2-dependent SUMO modification is required in development of all major trophoblast lineages. SENP2 regulates sumoylation of Mdm2 which controls p53 activities critical for G-S transition of mitotic division and endoreduplication in trophoblast proliferation and differentiation, respectively
physiological function
leptin treatment of C2C12 myotubes causes signal transducer and activator of transcription STAT3 to bind to the Senp2 promoter, inducing its expression. When Senp2 is knocked down in myotubes, leptin-induced expression of fatty acid oxidation-associated enzymes and prolonged increase of fatty acid oxidation are suppressed, but rapid increase of fatty acid oxidation is unaffected. Leptin-induced expression of fatty acid oxidation-associated enzymes is not observed in muscle tissue of SENP2 knockout mice
malfunction
-
SENP2 ablation disturbs the p53-Mdm2 pathway, affecting the expansion of trophoblast progenitors and their maturation
malfunction
-
enzyme SENP2 knockout MEF cells show increased glucose uptake and lactate production along with decreased ATP levels. SENP2 knockout embryonic fibroblasts exhibit increased levels of phosphorylated AKT. Inhibiting AKT phosphorylation by LY294002 rescues the phenotype induced by SENP2 deficiency in embryonic fibroblasts. Knockout of SENP2 leads to increased aerobic glycolysis in MEF cells
physiological function
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SENP2 in mice reveals its essential role in development of all three trophoblast layers. SENP2 has a specific role in the G-S transition, which is required for mitotic and endoreduplication cell cycles in trophoblast proliferation and differentiation, respectively
physiological function
-
enzyme SENP2 represses glycolysis and shifts glucose metabolic strategy, in part through inhibition of AKT phosphorylation, function of SENP2 in regulating glucose metabolism, overview
physiological function
-
nuclear factor-kappaB-mediated increase in the expression of SENP2 promotes the recruitment of peroxisome proliferator-activated receptors PPARdelta and PPARgamma, through deSUMOylation of PPARs, to the promoters of the genes involved in fatty acid oxidation, such as carnitine-palmitoyl transferase-1 and long-chain acyl-CoA synthetase 1. Enzyme overexpression substantially increases fatty acid oxidation in C2C12 myotubes
physiological function
-
the broad deSUMOylation activity of the enzyme in vitro is essential for embryonic heart development, essential role of small ubiquitin-like modifier-specific protease 2 in myostatin expression and myogenesis, overview. Enzyme SENP2 regulates the transcription of myostatin mainly through deSUMOylation of MEF2A. MEF2A mediates SENP2 activity on the myostatin promoter involving the MEF2 binding site. Enzyme SENP2 inhibits skeletal myogenesis
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Jiang, M.; Chiu, S.Y.; Hsu, W.
SUMO-specific protease 2 in Mdm2-mediated regulation of p53
Cell Death Differ.
18
1005-1015
2011
Mus musculus
brenda
Chung, S.S.; Ahn, B.Y.; Kim, M.; Choi, H.H.; Park, H.S.; Kang, S.; Park, S.G.; Kim, Y.B.; Cho, Y.M.; Lee, H.K.; Chung, C.H.; Park, K.S.
Control of adipogenesis by the SUMO-specific protease SENP2
Mol. Cell. Biol.
30
2135-2146
2010
Mus musculus (Q91ZX6)
brenda
Kang, X.; Qi, Y.; Zuo, Y.; Wang, Q.; Zou, Y.; Schwartz, R.J.; Cheng, J.; Yeh, E.T.
SUMO-specific protease 2 is essential for suppression of polycomb group protein-mediated gene silencing during embryonic development
Mol. Cell
38
191-201
2010
Mus musculus (Q91ZX6)
brenda
Chiu, S.Y.; Asai, N.; Costantini, F.; Hsu, W.
SUMO-specific protease 2 is essential for modulating p53-Mdm2 in development of trophoblast stem cell niches and lineages
PLoS Biol.
6
e310
2008
Mus musculus
brenda
Koo, Y.D.; Choi, J.W.; Kim, M.; Chae, S.; Ahn, B.Y.; Kim, M.; Oh, B.C.; Hwang, D.; Seol, J.H.; Kim, Y.B.; Park, Y.J.; Chung, S.S.; Park, K.S.
SUMO-specific protease 2 (SENP2) is an important regulator of fatty acid metabolism in skeletal muscle
Diabetes
64
2420-2431
2015
Mus musculus
brenda
Qi, Y.; Zuo, Y.; Yeh, E.T.; Cheng, J.
An essential role of small ubiquitin-like modifier (SUMO)-specific protease 2 in myostatin expression and myogenesis
J. Biol. Chem.
289
3288-3293
2014
Mus musculus, Mus musculus C57BL/6
brenda
Tang, S.; Huang, G.; Tong, X.; Xu, L.; Cai, R.; Li, J.; Zhou, X.; Song, S.; Huang, C.; Cheng, J.
Role of SUMO-specific protease 2 in reprogramming cellular glucose metabolism
PLoS ONE
8
e63965
2013
Homo sapiens, Mus musculus
brenda
Zheng, Q.; Cao, Y.; Chen, Y.; Wang, J.; Fan, Q.; Huang, X.; Wang, Y.; Wang, T.; Wang, X.; Ma, J.; Cheng, J.
Senp2 regulates adipose lipid storage by de-SUMOylation of Setdb1
J. Mol. Cell Biol.
10
258-266
2018
Mus musculus (Q91ZX6)
brenda
Koo, Y.D.; Lee, J.S.; Lee, S.A.; Quaresma, P.G.F.; Bhat, R.; Haynes, W.G.; Park, Y.J.; Kim, Y.B.; Chung, S.S.; Park, K.S.
SUMO-specific protease 2 mediates leptin-induced fatty acid oxidation in skeletal muscle
Metab. Clin. Exp.
95
27-35
2019
Mus musculus (Q91ZX6)
brenda
Maruyama, E.O.; Lin, H.; Chiu, S.Y.; Yu, H.M.; Porter, G.A.; Hsu, W.
Extraembryonic but not embryonic SUMO-specific protease 2 is required for heart development
Sci. Rep.
6
20999
2016
Mus musculus (Q91ZX6)
brenda