肿瘤坏死因子受体作用因子3(TRAF3)结构及生物学功能

目前在哺乳动物中发现6个肿瘤坏死因子受体作用因子(TNF receptor associated factors,TRAFs)家族成员,它们主要参与TNF受体家族信号通路.这些TRAF成员在C末端有螺旋卷曲结构和保守的TRAF结构域.TRAF3是TRAF家族中功能最为多样化的成员之一.1996年对TRAF3基因敲除小鼠进行研究发现,小鼠在出生早期死亡,这阻碍了TRAF3的生物学功能进一步研究,另一方面也证实了TRAF3在出生后发育以及维持正常的免疫系统功能方面有着重要生物学功能.10年后研究发现,TRAF3的缺失能够导致非经典NF-κB信号通路激活,这使得TRAF3在该信号通路中的功能得到了进一步的阐述.最近研究表明,TRAF3不仅能够负向调节NF-κB和MAPK信号通路,还能够正向调节Ⅰ型干扰素的产生.通过研究还发现,TRAF3可能存在着负向调节钙调蛋白磷酸酶活性的新功能.因此,研究TRAF3在免疫信号通路中的作用以及与之相关的病毒疾病具有重要的意义.

The Structure and Biological Function of TRAF3

The mammalian TNF receptor associated factor(TRAF) family consists of six members that are predominantly involved in the signal transduction of the TNF-receptor superfamily.The C-terminus of TRAFs consists of a coiled-coil domain followed by a conserved receptor-interacting domain(TRAF-C).TRAF3 is a less characterized member in the TRAFs family.Targeted disruption of TRAF3 led to postnatal lethality,manifesting the important function of TRAF3s.Studies also indicated that TRAF3 was required for postnatal development and for the competence of immune system.Recent reports showed that TRAF3 disruption caused non-canonical NF-κB activation,implying the negatively regulation of NF-κB and MAPK signals by TRAF3 and upregulation of type I IFN production.We found that TRAF3 downregulated CN-NFAT signal pathway,suggesting a role of TRAF3 immunological and viral infection diseases.