TNF-α信号传导通路的分子机理

Molecular Mechanism of TNF-α Signal Transduction

肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-α)是一种具有多效生物学效应的细胞因子.TNF的生物学效应都是通过细胞表面的2种TNF受体(TNFR)引发,其信号传导通路主要包括caspase家族介导的细胞凋亡、衔接蛋白TRAF介导的转录因子NF-κB和JNK蛋白激酶的活化.TNFR1和TNFR2的生物学功能不是独立的,许多生物学活性由二者共同完成.3条信号传导通路之间及各通路内部含有各种调节机制,使TNF的各种生物学功能协调发挥出来.本文评述了3条信号传导通路最新进展、关键激酶的研究状况及其在整个信号网络中的作用机理,如IKK的激活以及重要的信号转导分子RIP、TRAF2、TRUSS的结构、相互作用的方式等.

Tumor necrosis factor（TNF）-alpha is a pleiotropic cytokine,which exerts its biological functions by interactions with two members of the TNF receptor（TNFR）. Both receptors trigger several signal transduction pathways,including apoptosis mediated by caspase family , the activation of NF-κB, and JNK mediated by scaffolding protein TRAF. TNFR1 and TNFR2 perform their functions in a cooperative rather than independent manner. There are various regulation mechanisms existing in the three signal transduction pathways, which contributes to the coordinative effect of TNF-α. This article reviews the current progress on the studies of these signal transduction pathways, as well as the critical kinases and involved mechanism of action on the whole signal network, such as the activation of IKK, and the structure and interactive mold of some important signal molecules RIP, TRAF2 and TRUSS.