Natoli G, Costanzo A, Ianni A, Templeton D J, Woodgett J R, Balsano C, Levrero M
Fondazione Andrea Cesalpino and Istituto di I Clinica Medica, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy.
Science. 1997 Jan 10;275(5297):200-3. doi: 10.1126/science.275.5297.200.
Interaction of the p55 tumor necrosis factor receptor 1 (TNF-R1)-associated signal transducer TRADD with FADD signals apoptosis, whereas the TNF receptor-associated factor 2 protein (TRAF2) is required for activation of the nuclear transcription factor nuclear factor kappa B. TNF-induced activation of the stress-activated protein kinase (SAPK) was shown to occur through a noncytotoxic TRAF2-dependent pathway. TRAF2 was both sufficient and necessary for activation of SAPK by TNF-R1; conversely, expression of a dominant-negative FADD mutant, which blocks apoptosis, did not interfere with SAPK activation. Therefore, SAPK activation occurs through a pathway that is not required for TNF-R1-induced apoptosis.
p55肿瘤坏死因子受体1（TNF-R1）相关信号转导分子TRADD与FADD相互作用可传导凋亡信号，而核转录因子核因子κB的激活则需要肿瘤坏死因子受体相关因子2蛋白（TRAF2）。肿瘤坏死因子（TNF）诱导的应激激活蛋白激酶（SAPK）激活是通过一条非细胞毒性的、依赖TRAF2的途径实现的。TRAF2对于TNF-R1激活SAPK而言既是充分的也是必要的；相反，能阻断凋亡的显性负性FADD突变体的表达并不干扰SAPK的激活。因此，SAPK激活是通过一条TNF-R1诱导凋亡所不需要的途径发生的。
