5月19日，《细胞》子刊《发育细胞》杂志发表了中国科学院上海生命科学研究院生物化学与细胞生物学研究所王纲研究组的一项最新研究成果，该项研究工作发现了中介体复合物(Mediator Complex)的Med23亚基在Insulin诱导脂肪细胞分化过程中的重要作用。
据介绍，脂肪细胞分化过程受到众多的信号通路和转录因子调节，其中一条十分重要的通路是Insulin信号通路，但Insulin通路的信号是如何传导至核内的转录网络还不十分清楚。在Insulin信号转导途径中，核内蛋白Krox20是已被发现的控制脂肪细胞分化过程的最早的转录因子，但Krox20如何被Insulin调控的具体机制也不清楚。
王纲研究组的博士生汪炜和助研黄璐博士（共同第一作者）通过一系列的分子与细胞生物学实验，证明了Mediator复合物的Med23亚基和它的相互作用蛋白Elk1都是影响脂肪细胞分化的重要调节因子。这项研究发现，无论是敲除Med23或者Elk1，都会明显抑制脂肪细胞分化过程；Med23通过控制Krox20的基因转录水平来调节脂肪细胞分化；在Med23缺失的细胞中过表达Krox20能够挽救因Med23缺失而引起的分化缺陷。他们还通过进一步的生物化学实验具体分析了Med23控制Krox20的分子机制。
该工作揭示了Med23-Elk1的相互作用是连接Insulin信号通路与核内基因转录网络的重要节点，为脂肪的生成提供了新的分子解释，为干预肥胖及相关疾病提供了一种新的可能性。
该项工作得到国家科技部、中国科学院和上海市科委的经费支持。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
