Vito P, Pellegrini L, Guiet C, D'Adamio L
T-cell Molecular Biology Unit, Laboratory of Cellular and Molecular Immunology, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 1999 Jan 15;274(3):1533-40. doi: 10.1074/jbc.274.3.1533.
ALG-2 is a 22-kDa calcium-binding protein necessary for cell death induced by different stimuli in 3DO T-cell hybridoma. 3DO cell clones depleted of ALG-2 protein exhibit normal caspases activation, suggesting that ALG-2 function is required downstream or is independent of caspase proteases activity for apoptosis to occur. Using the yeast two-hybrid screening system, we have isolated and characterized the mouse cDNA encoding for ALG-2 interacting protein 1 (AIP1), a novel protein that interacts with ALG-2. ALG-2 and AIP1 colocalize in the cytosol and the presence of calcium is an indispensable requisite for their association. Sequence alignment shows that AIP1 is highly similar to BRO1, a yeast protein related to components of the Pkc1p-MAP kinase cascade. Overexpression of a truncated form of AIP1 protects two different cell types from death induced by trophic factors withdrawal; thus, our data indicate that AIP1 cooperates with ALG-2 in executing the calcium-dependent requirements along the cell death pathway.
ALG-2是一种22 kDa的钙结合蛋白，是3DO T细胞杂交瘤中不同刺激诱导细胞死亡所必需的。缺乏ALG-2蛋白的3DO细胞克隆表现出正常的半胱天冬酶激活，这表明ALG-2功能在细胞凋亡发生时是在半胱天冬酶蛋白酶活性的下游所必需的，或者与其无关。利用酵母双杂交筛选系统，我们分离并鉴定了编码与ALG-2相互作用蛋白1（AIP1）的小鼠cDNA，AIP1是一种与ALG-2相互作用的新型蛋白。ALG-2和AIP1共定位于细胞质中，钙的存在是它们结合所必需的条件。序列比对显示，AIP1与BRO1高度相似，BRO1是一种与Pkc1p-MAP激酶级联成分相关的酵母蛋白。截短形式的AIP1的过表达保护两种不同的细胞类型免受营养因子撤除诱导的死亡；因此，我们的数据表明，AIP1与ALG-2协同作用，在细胞死亡途径中执行钙依赖性需求。
