Jan Yiwen, Matter Michelle, Pai Jih-tung, Chen Yen-Liang, Pilch Jan, Komatsu Masanobu, Ong Edgar, Fukuda Minoru, Ruoslahti Erkki
Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cell. 2004 Mar 5;116(5):751-62. doi: 10.1016/s0092-8674(04)00204-1.
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.
信号之间的微妙平衡调节着细胞存活。其中一组信号源自整合素介导的细胞与细胞外基质（ECM）的黏附。细胞与ECM的附着丧失会导致凋亡，这一过程称为失巢凋亡。在寻找参与细胞黏附依赖性失巢凋亡调节的蛋白质时，我们鉴定出了Bit1，一种在凋亡过程中释放到细胞质中的线粒体蛋白。细胞质中的Bit1与AES（一种小的类Groucho/转导素样分裂增强子（TLE）蛋白）形成复合物，并诱导具有非半胱天冬酶依赖性凋亡特征的细胞死亡。细胞与纤连蛋白的附着可抵消Bit1和AES的凋亡作用。增加Bit1的表达会增强失巢凋亡，而抑制其表达则会降低失巢凋亡。因此，我们阐明了一条整合素控制的途径，该途径至少部分地负责细胞与ECM相互作用对细胞存活的影响。
Zotero 插件