Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel D V
Tularik Inc., South San Francisco, California 94080, USA.
Nature. 1996 Oct 3;383(6599):443-6. doi: 10.1038/383443a0.
Many cytokines signal through different cell-surface receptors to activate the transcription factor NF-kappaB. Members of the TRAF protein family have been implicated in the activation of NF-kappaB by the tumour-necrosis factor (TNF)-receptor superfamily. Here we report the identification of a new TRAF family member, designated TRAF6. When overexpressed in human 293 cells, TRAF6 activates NF-kappaB. A dominant-negative mutant of TRAF6 inhibits NF-kappaB activation signalled by interleukin-1 (IL-1) but not by TNF. IL-1 treatment of 293 cells induces the association of TRAF6 with IRAK, a serine/threonine kinase that is rapidly recruited to the IL-1 receptor after IL-1 induction. These findings indicate that TRAF proteins may function as signal transducers for distinct receptor families and that TRAF6 participates in IL-1 signalling.
许多细胞因子通过不同的细胞表面受体发出信号，以激活转录因子NF-κB。TRAF蛋白家族的成员已被证实参与肿瘤坏死因子（TNF）受体超家族对NF-κB的激活过程。在此，我们报告了一个新的TRAF家族成员的鉴定，命名为TRAF6。当在人293细胞中过表达时，TRAF6可激活NF-κB。TRAF6的一个显性负性突变体可抑制白介素-1（IL-1）介导的NF-κB激活，但不影响TNF介导的激活。用IL-1处理293细胞可诱导TRAF6与IRAK（一种丝氨酸/苏氨酸激酶，在IL-1诱导后迅速募集到IL-1受体）结合。这些发现表明，TRAF蛋白可能作为不同受体家族的信号转导分子发挥作用，且TRAF6参与IL-1信号传导。
