Xu Q, Reed J C
Burnham Institute Program on Apoptosis and Cell Death Research La Jolla, California 92037, USA.
Mol Cell. 1998 Feb;1(3):337-46. doi: 10.1016/s1097-2765(00)80034-9.
The mammalian proapoptotic protein Bax confers a lethal phenotype when expressed in yeast. By exploiting this phenotype, we have identified a novel human Bax inhibitor, BI-1. BI-1 is an evolutionarily conserved integral membrane protein containing multiple membrane-spanning segments and is predominantly localized to intracellular membranes, similar to Bcl-2 family proteins. Moreover, BI-1 can interact with Bcl-2 and Bcl-XL but Bax or Bak, as demonstrated by in vivo cross-linking and coimmunoprecipitation studies. When overexpressed in mammalian cells, BI-1 suppressed apoptosis included by Bax, etoposide, staurosporine, and growth factor deprivation, but not by Fas (CD95). Conversely, BI-1 antisense induced apoptosis. BI-1 thus represents a new type of regulator of cell death pathways controlled by Bcl-2 and Bax.
哺乳动物促凋亡蛋白Bax在酵母中表达时会赋予致死表型。通过利用这一表型，我们鉴定出一种新型的人类Bax抑制剂BI-1。BI-1是一种进化上保守的整合膜蛋白，含有多个跨膜区段，主要定位于细胞内膜，类似于Bcl-2家族蛋白。此外，体内交联和免疫共沉淀研究表明，BI-1可与Bcl-2和Bcl-XL相互作用，但不与Bax或Bak相互作用。当在哺乳动物细胞中过表达时，BI-1可抑制由Bax、依托泊苷、星形孢菌素和生长因子剥夺所诱导的凋亡，但不能抑制由Fas（CD95）诱导的凋亡。相反，BI-1反义核酸可诱导凋亡。因此，BI-1代表了一种由Bcl-2和Bax控制的细胞死亡途径的新型调节因子。
