Schnurri-2 controls BMP-dependent adipogenesis via interaction with Smad proteins.
Adipocyte differentiation is an important component of obesity, but how hormonal cues mediate adipocyte differentiation remains elusive. BMP stimulates in vitro adipocyte differentiation, but the role of BMP in adipogenesis in vivo is unknown. Drosophila Schnurri (Shn) is required for the signaling of Decapentaplegic, a Drosophila BMP homolog, via interaction with the Mad/Medea transcription factors. Vertebrates have three Shn orthologs, Shn-1, -2, and -3. Here, we report that Shn-2(-/-) mice have reduced white adipose tissue and that Shn-2(-/-) mouse embryonic fibroblasts cannot efficiently differentiate into adipocytes in vitro. Shn-2 enters the nucleus upon BMP-2 stimulation and, in cooperation with Smad1/4 and C/EBPalpha, induces the expression of PPARgamma2, a key transcription factor for adipocyte differentiation. Shn-2 directly interacts with both Smad1/4 and C/EBPalpha on the PPARgamma2 promoter. These results indicate that Shn-2-mediated BMP signaling has a critical role in adipogenesis.
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Wanzhu
W
Jin
Tsuyoshi
T
Takagi
Shin-nosuke
SN
Kanesashi
Toshihiro
T
Kurahashi
Teruaki
T
Nomura
Jun
J
Harada
Shunsuke
S
Ishii
D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology / Q000502:physiology; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D008060:Lipodystrophy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051898:Smad1 Protein / Q000502:physiology*; D051901:Smad4 Protein / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D022763:CCAAT-Enhancer-Binding Protein-alpha; D004268:DNA-Binding Proteins; C490430:Hivep2 protein, mouse; D047495:PPAR gamma; D012333:RNA, Messenger; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D016212:Transforming Growth Factor beta