Zhang Yi, Zhao Xiaoping, Yang Fajun
Department of Medicine, Developmental and Molecular Biology, Diabetes Research and Training Center, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx NY 10461, USA.
J Biochem Pharmacol Res. 2013 Mar;1(1):51-55.
The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understanding on the biological functions of Mediator remains incomplete, research in the past decade has revealed an important role of Mediator in regulating lipid metabolism. Such function of Mediator is dependent on specific transcription factors, including peroxisome proliferator-activated receptor-gamma (PPARγ) and sterol regulatory element-binding proteins (SREBPs), which represent the master regulators of lipid metabolism. The medical significance of these findings is apparent, as aberrant lipid metabolism is intimately linked to major human diseases, such as type 2 diabetes and cardiovascular disease. Here, we briefly review the functions and molecular mechanisms of Mediator in regulation of lipid metabolism.
基因表达的精确调控对于所有生物过程都至关重要。除了DNA结合转录因子外,众多转录辅因子在真核细胞中为基因转录调控增添了另一层调节作用。这类转录辅因子之一是高度保守的中介体复合物,它有多个亚基,并通过与相关转录因子直接相互作用参与各种生物过程。尽管目前对中介体生物学功能的理解仍不完整,但过去十年的研究揭示了中介体在调节脂质代谢中的重要作用。中介体的这种功能依赖于特定的转录因子,包括过氧化物酶体增殖物激活受体γ(PPARγ)和固醇调节元件结合蛋白(SREBP),它们是脂质代谢的主要调节因子。这些发现的医学意义显而易见,因为脂质代谢异常与主要人类疾病密切相关,如2型糖尿病和心血管疾病。在此,我们简要综述中介体在调节脂质代谢中的功能和分子机制。