Research News

New Study Reveals the “Yin-Yang” Function of MED23

Source: Time: 2012-09-17
The Mediator complex functions as a control center, orchestrating diverse signaling, gene activities, and physiological processes. How different subunits of the Mediator complex determine distinct cell fates remains to be fully elucidated. Now researchers from Chinese Academy of Sciences demonstrates that Mediator MED23 can act as a two-way molecular switch in directing the smooth muscle cell vs. adipocyte differentiation, by fine-tuning the balance between RhoA/MAL and Ras/ELK1 signaling pathways.
 
Dr. WANG Gang’s group from the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences previously showed that Mediator MED23 is a positive regulator linking insulin signaling to the adipogenesis transcriptional cascade (Wang et al. Dev Cell, 2009). Now they observed in this study that MED23 can act as a restrictive regulator for RhoA/MAL signaling and smooth muscle cell (SMC) differentiation. The presence or absence of MED23 oppositely regulated two groups of genes, the RhoA/MAL targeted cytoskeletal/smooth muscle genes vs. Ras/ELK1 targeted growth/adipogenic genes. Further, Med23-deficiency facilitates SMC differentiation but represses adipocyte differentiation from the multipotent mesenchymal stem cells. Biochemistry analysis revealed that the presence of MED23 favors ELK1-SRF complex binding at SMC gene promoters for repression, whereas the absence of MED23 favors MAL-SRF complex binding at SMC gene promoters for activation. Remarkably, this SMC-promoting effect by Med23-deficiency can be recapitulated in the early embryogenesis of zebrafish. Therefore, MED23 seems to control a “Ying-Yang” switch in modulating the alternative cell fates (smooth muscle cells vs. adipocytes) of the mesenchymal stem cells.
 
This study contributes a better understanding and a possible therapeutic target for the smooth muscle- and fat-related diseases, given that the imbalance of fat and smooth muscle tissue is often involved in many metabolic and cardiovascular diseases such as obesity, diabetes, atherosclerosis, and hypertension.
 
This study was just published in Genes and Development, and it was supported by grants from the Ministry of Science and Technology, Chinese Academy of Sciences, the National Natural Science Foundation of China and Science and Technology Commission of Shanghai Municipality.
 
CONTACT:
WANG Gang
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Email: gwang22@sibs.ac.cn Tel: 86-21-54921083
 
A schematic model for Mediator MED23 in controlling the balance between Ras/ELK1 and RhoA/MAL signaling (Image provided by Dr. Gang Wang)
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