Tan K O, Tan K M, Chan S L, Yee K S, Bevort M, Ang K C, Yu V C
Institute of Molecular and Cell Biology, 30 Medical Dr., Singapore 117609, Republic of Singapore.
J Biol Chem. 2001 Jan 26;276(4):2802-7. doi: 10.1074/jbc.M008955200. Epub 2000 Nov 1.
A novel Bax-associating protein, named MAP-1 (Modulator of Apoptosis), has been identified in a yeast two-hybrid screen. MAP-1 contains a BH3-like (BH: Bcl-2 homology) motif and mediates caspase-dependent apoptosis in mammalian cells when overexpressed. MAP-1 homodimerizes and associates with the proapoptotic Bax and the prosurvival Bcl-2 and Bcl-X(L) of the Bcl-2 family in vitro and in vivo in mammalian cells. Mutagenesis analyses revealed that the BH3-like domain in MAP-1 is not required for its association with Bcl-X(L) but is required for association with Bax and for mediating apoptosis. Interestingly, in contrast to other Bax-associating proteins such as Bcl-X(L) and Bid, which require the BH3 and BH1 domains of Bax, respectively, for binding, the binding of MAP-1 to Bax appears to require all three BH domains (BH1, BH2, and BH3) of Bax, because point mutation of the critical amino acid in any one of these domains is sufficient to abolish its binding to MAP-1. These data suggest that MAP-1 mediates apoptosis through a mechanism that involves binding to Bax.
在酵母双杂交筛选中鉴定出一种名为MAP-1（凋亡调节因子）的新型Bax相关蛋白。MAP-1含有一个BH3样（BH：Bcl-2同源性）基序，过表达时在哺乳动物细胞中介导半胱天冬酶依赖性凋亡。在体外和体内哺乳动物细胞中，MAP-1可形成同源二聚体，并与促凋亡的Bax以及Bcl-2家族的促生存蛋白Bcl-2和Bcl-X(L)相互作用。诱变分析表明，MAP-1中的BH3样结构域与其与Bcl-X(L)的相互作用无关，但与Bax的相互作用以及介导凋亡有关。有趣的是，与其他分别需要Bax的BH3和BH1结构域进行结合的Bax相关蛋白（如Bcl-X(L)和Bid）不同，MAP-1与Bax的结合似乎需要Bax的所有三个BH结构域（BH1、BH2和BH3），因为这些结构域中任何一个关键氨基酸的点突变都足以消除其与MAP-1的结合。这些数据表明，MAP-1通过一种涉及与Bax结合的机制介导凋亡。
