A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors

Yiwen Jan, Michelle Matter, Jih Tung Pai, Yen Liang Chen, Jan Pilch, Masanobu Komatsu, Edgar Ong, Minoru Fukuda, Erkki Ruoslahti

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)751-762
Number of pages12
JournalCell
Volume116
Issue number5
DOIs
StatePublished - Mar 5 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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