5月19日，《細(xì)胞》子刊《發(fā)育細(xì)胞》雜志發(fā)表了中國(guó)科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所王綱研究組的一項(xiàng)最新研究成果,，該項(xiàng)研究工作發(fā)現(xiàn)了中介體復(fù)合物(Mediator Complex)的Med23亞基在Insulin誘導(dǎo)脂肪細(xì)胞分化過程中的重要作用,。
據(jù)介紹，脂肪細(xì)胞分化過程受到眾多的信號(hào)通路和轉(zhuǎn)錄因子調(diào)節(jié),，其中一條十分重要的通路是Insulin信號(hào)通路,，但I(xiàn)nsulin通路的信號(hào)是如何傳導(dǎo)至核內(nèi)的轉(zhuǎn)錄網(wǎng)絡(luò)還不十分清楚。在Insulin信號(hào)轉(zhuǎn)導(dǎo)途徑中,，核內(nèi)蛋白Krox20是已被發(fā)現(xiàn)的控制脂肪細(xì)胞分化過程的最早的轉(zhuǎn)錄因子,，但Krox20如何被Insulin調(diào)控的具體機(jī)制也不清楚。
王綱研究組的博士生汪煒和助研黃璐博士（共同第一作者）通過一系列的分子與細(xì)胞生物學(xué)實(shí)驗(yàn),，證明了Mediator復(fù)合物的Med23亞基和它的相互作用蛋白Elk1都是影響脂肪細(xì)胞分化的重要調(diào)節(jié)因子,。這項(xiàng)研究發(fā)現(xiàn)，無論是敲除Med23或者Elk1,，都會(huì)明顯抑制脂肪細(xì)胞分化過程,；Med23通過控制Krox20的基因轉(zhuǎn)錄水平來調(diào)節(jié)脂肪細(xì)胞分化；在Med23缺失的細(xì)胞中過表達(dá)Krox20能夠挽救因Med23缺失而引起的分化缺陷,。他們還通過進(jìn)一步的生物化學(xué)實(shí)驗(yàn)具體分析了Med23控制Krox20的分子機(jī)制,。
該工作揭示了Med23-Elk1的相互作用是連接Insulin信號(hào)通路與核內(nèi)基因轉(zhuǎn)錄網(wǎng)絡(luò)的重要節(jié)點(diǎn)，為脂肪的生成提供了新的分子解釋,，為干預(yù)肥胖及相關(guān)疾病提供了一種新的可能性,。
該項(xiàng)工作得到國(guó)家科技部、中國(guó)科學(xué)院和上海市科委的經(jīng)費(fèi)支持,。（生物谷Bioon.com）
生物谷推薦原始出處：
Developmental Cell, 19 May 2009 doi:10.1016/j.devcel.2009.04.006
Mediator MED23 Links Insulin Signaling to the Adipogenesis Transcription Cascade
Wei Wang1,4,Lu Huang1,4,Yan Huang1,Jing-wen Yin1,Arnold J. Berk2,Jeffrey M. Friedman3andGang Wang1,,
1 State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, ChineseAcademy of Sciences, Shanghai 200031, China
2 Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA
3 Laboratory of Molecular Genetics, Rockefeller University, New York, NY 10021, USA
4 These authors have contributed equally to this manuscript
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/EBP or PPAR. 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.
