细胞死亡途径的分子排序。Bcl-2和Bcl-xL在类CED-3凋亡蛋白酶的上游发挥作用。

Molecular ordering of the cell death pathway. Bcl-2 and Bcl-xL function upstream of the CED-3-like apoptotic proteases.

作者信息

Chinnaiyan A M, Orth K, O'Rourke K, Duan H, Poirier G G, Dixit V M

机构信息

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

出版信息

J Biol Chem. 1996 Mar 1;271(9):4573-6. doi: 10.1074/jbc.271.9.4573.

DOI:10.1074/jbc.271.9.4573

PMID:8617712

Abstract

Genetic analyses of Caenorhabditis elegans has identified three genes that function in the regulation of nematode cell death. Mammalian homologs of two of these genes, ced-9 and ced-3, have been identified and comprise proteins belonging to the Bcl-2 and ICE families, respectively. To date, it is unclear where the negative regulators, ced-9 and bcl-2, function relative to the death effectors, ced-3 and the mammalian ced-3 homologs, respectively. Here, the molecular order of the cell death pathway is defined. Our results establish that Bcl-2 and Bcl-xL function upstream of two members of the ICE/CED-3 family of cysteine proteases, Yama (CPP32/apopain) and ICE-LAP3 (Mch3).

摘要

对线虫的遗传分析已鉴定出三个参与线虫细胞死亡调控的基因。其中两个基因ced-9和ced-3的哺乳动物同源物已被鉴定出来，分别包含属于Bcl-2和ICE家族的蛋白质。迄今为止，尚不清楚负调控因子ced-9和bcl-2分别相对于死亡效应因子ced-3和哺乳动物ced-3同源物在何处发挥作用。在此，确定了细胞死亡途径的分子顺序。我们的结果表明，Bcl-2和Bcl-xL在半胱氨酸蛋白酶ICE/CED-3家族的两个成员Yama（CPP32/凋亡蛋白酶）和ICE-LAP3（Mch3）上游发挥作用。