Mediator MED23 links insulin signaling to the adipogenesis transcription cascade.
Adipocyte differentiation is orchestrated by multiple signaling pathways and a temporally regulated transcriptional cascade. However, the mechanisms by which insulin signaling is linked to this cascade remain unclear. Here we show that the Med23 subunit of the Mediator Complex and its interacting transcription factor Elk1 are critical regulators of adipogenesis. Med23(-/-) embryonic fibroblast cells were refractory to hormone-induced adipogenesis. Knockdown of either Med23 or Elk1, or overexpression of dominant-negative Elk1, inhibited adipogenesis. In the absence of either Elk1 or Med23, Krox20, an immediate early gene stimulated by insulin during adipogenesis, was uninducible. Moreover, the adipogenic defect in Med23-deficient cells was rescued by ectopic expression of Krox20 or one of its downstream factors, C/EBPbeta or PPARgamma. Mechanistically, the insulin-stimulated, Med23-deficient preinitiation complex failed to initiate robust transcription of Krox20. Collectively, our results suggest that Med23 serves as a critical link transducing insulin signaling to the transcriptional cascade during adipocyte differentiation.
Wang
Wei
W
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Huang
Lu
L
Huang
Yan
Y
Yin
Jing-wen
JW
Berk
Arnold J
AJ
Friedman
Jeffrey M
JM
Wang
Gang
G
D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D051767:Early Growth Response Protein 2 / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D053263:Gene Regulatory Networks; D005804:Genes, Lethal; D007328:Insulin / Q000378:metabolism*; D056892:Mediator Complex; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; C494113:Elk1 protein, mouse; D007328:Insulin; C541034:Med23 protein, mouse; D056892:Mediator Complex; D050807:ets-Domain Protein Elk-1