CED-4与CED-3和CED-9的相互作用：细胞死亡的分子框架。

Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death.

作者信息

Chinnaiyan A M, O'Rourke K, Lane B R, Dixit V M

机构信息

University of Michigan Medical School, Department of Pathology, Ann Arbor, MI 48109, USA.

出版信息

Science. 1997 Feb 21;275(5303):1122-6. doi: 10.1126/science.275.5303.1122.

DOI:10.1126/science.275.5303.1122

PMID:9027312

Abstract

Previous genetic studies of the nematode Caenorhabditis elegans identified three important components of the cell death machinery. CED-3 and CED-4 function to kill cells, whereas CED-9 protects cells from death. Here CED-9 and its mammalian homolog Bcl-xL (a member of the Bcl-2 family of cell death regulators) were both found to interact with and inhibit the function of CED-4. In addition, analysis revealed that CED-4 can simultaneously interact with CED-3 and its mammalian counterparts interleukin-1beta-converting enzyme (ICE) and FLICE. Thus, CED-4 plays a central role in the cell death pathway, biochemically linking CED-9 and the Bcl-2 family to CED-3 and the ICE family of pro-apoptotic cysteine proteases.

摘要

之前对线虫秀丽隐杆线虫的遗传学研究确定了细胞死亡机制的三个重要组成部分。CED-3和CED-4的作用是杀死细胞，而CED-9则保护细胞免于死亡。在这里发现，CED-9及其哺乳动物同源物Bcl-xL（细胞死亡调节因子Bcl-2家族的成员）都能与CED-4相互作用并抑制其功能。此外，分析表明，CED-4可以同时与CED-3及其哺乳动物对应物白细胞介素-1β转换酶（ICE）和FLICE相互作用。因此，CED-4在细胞死亡途径中起着核心作用，在生化上将CED-9和Bcl-2家族与CED-3和促凋亡半胱氨酸蛋白酶的ICE家族联系起来。