Heyninck K, Beyaert R
Unit for Molecular Signal Transduction in Inflammation, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, University of Ghent, K. L. Ledeganckstraat 35, Ghent, B-9000, Belgium.
Mol Cell Biol Res Commun. 2001 Sep;4(5):259-65. doi: 10.1006/mcbr.2001.0295.
The cytokine tumor necrosis factor (TNF) elicits a wide range of biological responses, including inflammation, cell proliferation, differentiation, and apoptosis. Although the molecular mechanisms of TNF signaling have been largely elucidated, the principle that regulates the balance of life and death is still unknown. This review will focus on the crosstalk that exists between proteins of the TNF receptor (TNF-R) signalosome, and which are involved in the initiation of nuclear factor kappa B (NF-kappaB) activation or apoptosis. At least four different mechanisms of regulation can be distinguished: (i) NF-kappaB-mediated induction of proteins of the TNF-R complex; (ii) NF-kappaB-independent protection against apoptosis by the TNF-R-associating factor 2 (TRAF2)-mediated recruitment of antiapoptotic proteins; (iii) dual activation of apoptosis and NF-kappaB by a single molecule; and (iv) amplification of the death signal by proteolytic inactivation of signaling proteins that are involved in NF-kappaB activation or cell survival.
细胞因子肿瘤坏死因子（TNF）引发广泛的生物学反应，包括炎症、细胞增殖、分化和凋亡。尽管TNF信号传导的分子机制已基本阐明，但调节生死平衡的原理仍不清楚。本综述将聚焦于TNF受体（TNF-R）信号体蛋白之间存在的相互作用，这些蛋白参与核因子κB（NF-κB）激活或凋亡的起始。至少可以区分出四种不同的调节机制：（i）NF-κB介导的TNF-R复合物蛋白诱导；（ii）TNF受体相关因子2（TRAF2）介导的抗凋亡蛋白募集对凋亡的NF-κB非依赖性保护；（iii）单个分子对凋亡和NF-κB的双重激活；以及（iv）通过参与NF-κB激活或细胞存活的信号蛋白的蛋白水解失活来放大死亡信号。
