A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors
A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors
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DOI：
10.1016/s0092-8674(04)00204-1
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发表时间：
2004-03-05
期刊：
影响因子：
64.5
通讯作者：
Ruoslahti, E
中科院分区：
文献类型：
--
作者：
Jan, YW;Matter, M;Ruoslahti, E
信号的微妙平衡调节细胞存活。这些信号中的一组来源于整合素介导的细胞与细胞外基质（ECM）的粘附。细胞与ECM的附着丧失导致细胞凋亡，这一过程称为失巢凋亡。在寻找参与失巢凋亡的细胞粘附依赖性调节的蛋白质时，我们确定了Bit 1，一种在细胞凋亡过程中释放到细胞质中的线粒体蛋白。细胞质Bit 1与AES形成复合物，AES是一种小的Groucho/转导素样分裂增强子（TLE）蛋白，并诱导具有半胱天冬酶非依赖性凋亡特征的细胞死亡。细胞附着到纤连蛋白抵消了Bit 1和AES的凋亡作用。增加Bit 1的表达增强失巢凋亡，而抑制表达减少it. Thus，我们已经阐明了一个整合素控制的途径，是，至少部分，负责细胞-ECM相互作用的细胞存活的影响。
A delicate balance of signals regulates cell survival. One set of these signals is derived from integrin-mediated cell adhesion to the extracellular matrix (ECM). Loss of cell attachment to the ECM causes apoptosis, a process known as anoikis. In searching for proteins involved in cell adhesion-dependent regulation of anoikis, we identified Bit1, a mitochondrial protein that is released into the cytoplasm during apoptosis. Cytoplasmic Bit1 forms a complex with AES, a small Groucho/transducin-like enhancer of split (TLE) protein, and induces cell death with characteristics of caspase-independent apoptosis. Cell attachment to fibronectin counteracts the apoptotic effect of Bit1 and AES. Increasing Bit1 expression enhances anoikis, while suppressing the expression reduces it. Thus, we have elucidated an integrin-controlled pathway that is, at least in part, responsible for the cell survival effects of cell-ECM interactions.