SUMO modification selectively regulates transcriptional activity of peroxisome-proliferator-activated receptor γ in C2C12 myotubes.
PPAR (peroxisome-proliferator-activated receptor) γ, a nuclear receptor, can be conjugated with SUMO (small ubiquitin-like modifier), which results in the negative regulation of its transcriptional activity. In the present study, we tested whether de-SUMOylation of PPARγ affects the expression of PPARγ target genes in mouse muscle cells and investigated the mechanism by which de-SUMOylation increases PPARγ transcriptional activity. We found that the SUMO-specific protease SENP2 [SUMO1/sentrin/SMT3 (suppressor of mif two 3 homologue 1)-specific peptidase 2] effectively de-SUMOylates PPARγ-SUMO conjugates. Overexpression of SENP2 in C2C12 cells increased the expression of some PPARγ target genes, such as FABP3 (fatty-acid-binding protein 3) and CD36 (fatty acid translocase), both in the absence and presence of rosiglitazone. In contrast, overexpression of SENP2 did not affect the expression of another PPARγ target gene ADRP (adipose differentiation-related protein). De-SUMOylation of PPARγ increased ChIP (chromatin immunoprecipitation) of both a recombinant PPRE (PPAR-response element) and endogenous PPREs of the target genes CD36 and FABP3, but ChIP of the PPRE in the ADRP promoter was not affected by SENP2 overexpression. In conclusion, these results indicate that SENP2 de-SUMOylates PPARγ in myotubes, and de-SUMOylation of PPARγ selectively increases the expression of some PPARγ target genes.
Chung
Sung Soo
SS
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea.
Ahn
Byung Yong
BY
Kim
Min
M
Kho
Jun Ho
JH
Jung
Hye Seung
HS
Park
Kyong Soo
KS
D000818:Animals; D018955:CD36 Antigens / Q000235:genetics; D002460:Cell Line; D003546:Cysteine Endopeptidases; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D051379:Mice; D009097:Multienzyme Complexes / Q000235:genetics / Q000502:physiology*; D018485:Muscle Fibers, Skeletal; D047495:PPAR gamma / Q000235:genetics*; D058207:Sumoylation / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation
D018955:CD36 Antigens; C493409:Fabp3 protein, mouse; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D009097:Multienzyme Complexes; D047495:PPAR gamma; D003546:Cysteine Endopeptidases; C439066:Senp2 protein, mouse