Hsu H, Huang J, Shu H B, Baichwal V, Goeddel D V
Tularik, Incorporated, South San Francisco, California 94080, USA.
Immunity. 1996 Apr;4(4):387-96. doi: 10.1016/s1074-7613(00)80252-6.
The death domain of tumor necrosis factor (TNF) receptor-1 (TNFR1) triggers distinct signaling pathways leading to apoptosis and NF-kappa B activation through its interaction with the death domain protein TRADD. Here, we show that TRADD interacts strongly with RIP, another death domain protein that was shown previously to associate with Fas antigen. We also show that RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process. Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis. However, expression of the death domain of RIP Induces apoptosis, but potently inhibits NF-kappa B activation by TNF. These results suggest that distinct domains of RIP participate in the TNF signaling cascades leading to apoptosis and NF-kappa B activation.
肿瘤坏死因子（TNF）受体-1（TNFR1）的死亡结构域通过与死亡结构域蛋白TRADD相互作用，触发导致细胞凋亡和核因子-κB激活的不同信号通路。在此，我们表明TRADD与RIP强烈相互作用，RIP是另一种死亡结构域蛋白，先前已证明其与Fas抗原相关。我们还表明RIP是一种丝氨酸-苏氨酸激酶，在TNF依赖的过程中被TRADD招募至TNFR1。完整RIP蛋白的过表达可诱导核因子-κB激活和细胞凋亡。然而，RIP死亡结构域的表达诱导细胞凋亡，但有力地抑制TNF介导的核因子-κB激活。这些结果表明，RIP的不同结构域参与了导致细胞凋亡和核因子-κB激活的TNF信号级联反应。
