鉴定BARD1作为促凋亡应激与p53依赖性凋亡之间的介质。

Identification of BARD1 as mediator between proapoptotic stress and p53-dependent apoptosis.

作者信息

Irminger-Finger I, Leung W C, Li J, Dubois-Dauphin M, Harb J, Feki A, Jefford C E, Soriano J V, Jaconi M, Montesano R, Krause K H

机构信息

Biology of Aging Laboratory, Department of Geriatrics, Geneva, Switzerland.

出版信息

Mol Cell. 2001 Dec;8(6):1255-66. doi: 10.1016/s1097-2765(01)00406-3.

DOI:10.1016/s1097-2765(01)00406-3

PMID:11779501

Abstract

The BRCA1-associated protein BARD1 is a putative tumor suppressor. We suggest that BARD1 is a mediator of apoptosis since (1) cell death in vivo (ischemic stroke) and in vitro is accompanied by increased levels of BARD1 protein and mRNA; (2) overexpression of BARD1 induces cell death with all features of apoptosis; and (3) BARD1-repressed cells are defective for the apoptotic response to genotoxic stress. The proapoptotic activity of BARD1 involves binding to and elevations of p53. BRCA1 is not required for but partially counteracts apoptosis induction by BARD1. A tumor-associated mutation Q564H of BARD1 is defective in apoptosis induction, thus suggesting a role of BARD1 in tumor suppression by mediating the signaling from proapoptotic stress toward induction of apoptosis.

摘要

与乳腺癌1号基因（BRCA1）相关的蛋白BARD1是一种假定的肿瘤抑制因子。我们认为BARD1是细胞凋亡的介导因子，因为：（1）体内（缺血性中风）和体外的细胞死亡均伴随着BARD1蛋白和mRNA水平的升高；（2）BARD1的过表达诱导具有凋亡所有特征的细胞死亡；（3）BARD1表达受抑制的细胞对基因毒性应激的凋亡反应存在缺陷。BARD1的促凋亡活性涉及与p53结合并使其水平升高。BRCA1并非BARD1诱导凋亡所必需，但能部分抵消BARD1的凋亡诱导作用。BARD1的一个肿瘤相关突变Q564H在凋亡诱导方面存在缺陷，因此提示BARD1通过介导从促凋亡应激到凋亡诱导的信号传导在肿瘤抑制中发挥作用。