Hegde R, Srinivasula S M, Ahmad M, Fernandes-Alnemri T, Alnemri E S
Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
J Biol Chem. 1998 Apr 3;273(14):7783-6. doi: 10.1074/jbc.273.14.7783.
We identified and cloned a novel murine member of the pro-apoptotic Bcl-2 family. This protein, designated Blk, is structurally and functionally related to human Bik and localized to the mitochondrial membrane. Blk contains a conserved BH3 domain and can interact with the anti-apoptotic proteins Bcl-2 and Bcl-xL. Ectopic expression of Blk in mammalian cells induces apoptosis, which can be inhibited by mutations in the BH3 domain and by overexpression of Bcl-2 or Bcl-xL but not by CrmA. The apoptotic activity of Blk is also inhibited by a dominant negative caspase-9, suggesting that Blk induces apoptosis through activation of the cytochrome c-Apaf-1-caspase-9 pathway.
我们鉴定并克隆了促凋亡Bcl-2家族的一个新型小鼠成员。这种蛋白质命名为Blk，在结构和功能上与人类Bik相关，并定位于线粒体膜。Blk含有一个保守的BH3结构域，可与抗凋亡蛋白Bcl-2和Bcl-xL相互作用。在哺乳动物细胞中异位表达Blk可诱导细胞凋亡，这种凋亡可被BH3结构域的突变以及Bcl-2或Bcl-xL的过表达所抑制，但不能被CrmA抑制。Blk的凋亡活性也被显性负性caspase-9所抑制，这表明Blk通过激活细胞色素c-Apaf-1-caspase-9途径诱导细胞凋亡。
