TY - JOUR
T1 - A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors
AU - Jan, Yiwen
AU - Matter, Michelle
AU - Pai, Jih Tung
AU - Chen, Yen Liang
AU - Pilch, Jan
AU - Komatsu, Masanobu
AU - Ong, Edgar
AU - Fukuda, Minoru
AU - Ruoslahti, Erkki
N1 - Funding Information:
We thank Drs. Guy Salvesen and Stefano Stifani for cDNA clones; Dr. Webster Cavenee for support (Y.-L.C.); and Drs. Guy Salvesen, Eva Engvall, Steve Frisch, Jaime Pascual, Elena Pasquale, and Kristiina Vuori for helpful discussions. This work was supported by grants CA82713 and CA79984 (to E.R.), grant CA33000 (to M.F.), and CA 30199 (Cancer Center Support Grant) from NCI.
PY - 2004/3/5
Y1 - 2004/3/5
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(04)00204-1
DO - 10.1016/S0092-8674(04)00204-1
M3 - Article
C2 - 15006356
AN - SCOPUS:1542328956
SN - 0092-8674
VL - 116
SP - 751
EP - 762
JO - Cell
JF - Cell
IS - 5
ER -