cAMP-CREB信号转录通路新成员:CRTCs的研究进展

CRTCs:an Essential Coactivator Family of CREB Regulated Transcription

CRTCs(CREB Regulated Transcription Coactivator)是一个保守的真核蛋白质家族。作为CREB(CRE response element-binding protein)转录调控的必须共激活因子,CRTCs能与CREB结合并极强地增加后者的活性。同时作为cAMP-CREB信号转录通路的新成员,CRTCs能在细胞核质间穿梭并整合多个通路的信号,把细胞内外的信号直接传递到基因的转录活性。已经证实CRTC家族中的CRTC2在糖脂代谢调节及其相关疾病,特别是2型糖尿病的发生发展起着重要的作用。由于靶点明确,作用机制清楚,CRTC2及上游特异的调控因子有希望成为新的T2D治疗靶点。本文综述近年来CRTCs的研究成果,总结了CRTC2的发现、结构及分子机制。

Since its first description in 1987, CREB （CRE response element-binding protein） has been widely studied as a critical transcription factor to regulate many important genes with various functions. A recently identified pivotal CREB coactivator family, CRTCs is able to dramatically enhance CREB activity and involved in multiple CREB regulated physiological events. Among them, CRTC2 is the one best understood and its path/physiological function and regulatory mechanism have been well established in the last decade. Here, we will introduce the molecular structure and regulatory mechanism of CRTC family and then focus on the role of CRTC2 in obesity related diseases, especially type 2 diabetes.