Activation of Fas by FasL induces apoptosis by a mechanism that cannot be blocked by Bcl-2 or Bcl-xL

被引:276
作者
Huang, DCS
Hahne, M
Schroeter, M
Frei, K
Fontana, A
Villunger, A
Newton, K
Tschopp, J
Strasser, A
机构
[1] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
[2] Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland
[3] Univ Zurich Hosp, Dept Internal Med, Zurich, Switzerland
关键词
APO-1; CD95; signal transduction;
D O I
10.1073/pnas.96.26.14871
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Fas activation triggers apoptosis in many cell types. Studies with anti-fas antibodies have produced conflicting results on Fas signaling, particularly the role of the Bcl-2 family in this process. Comparison between physiological ligand and anti-Fas antibodies revealed that only extensive Fas aggregation, by membrane bound Fast or aggregated soluble Fast consistently triggered apoptosis, whereas antibodies could act as death agonists or antagonists. Studies on Fas signaling in cell lines and primary cells from transgenic mice revealed that FADD/MORT1 and caspase-8 were required for apoptosis. In contrast, Bcl-2 or Bcl-x(L) did not block Fast-induced apoptosis in lymphocytes or hepatocytes, demonstrating that signaling for cell death induced by Fas and the pathways to apoptosis regulated by the Bcl-2 family are distinct.
引用
收藏
页码:14871 / 14876
页数:6
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