Abstract
Bcl-2 protein is able to repress a number of apoptotic death programs. To investigate the mechanism of Bcl-2's effect, we examined whether Bcl-2 interacted with other proteins. We identified an associated 21 kd protein partner, Bax, that has extensive amino acid homology with Bcl-2, focused within highly conserved domains I and II. Bax is encoded by six exons and demonstrates a complex pattern of alternative RNA splicing that predicts a 21 kd membrane (α) and two forms of cytosolic protein (β and γ). Bax homodimerizes and forms heterodimers with Bcl-2 in vivo. Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line. Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.
Original language | English (US) |
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Pages (from-to) | 609-619 |
Number of pages | 11 |
Journal | Cell |
Volume | 74 |
Issue number | 4 |
DOIs | |
State | Published - Aug 27 1993 |
Externally published | Yes |
Bibliographical note
Funding Information:We thank David Hockenbery, Xiao-Ming Yin, Diane Merry, Gerry Li-nette. and Ed Wong for helpful suggestions and comments on the manuscript, Robinna Lorenz for murine tissue RNA, Deborah Veis for biotinylated 3Fll antibody, Jenny Ostrom for performing Northern hybridizations, Lisa Westfield for oligonucleotide synthesis, and Carolyn Davinroy for secretarial assistance. We are especially grateful for the expert technical assistance of Dave McCourt (Howard Hughes Medical Institute Protein Core Facility) for performing all the protein sequencing. 2. N. 0. is supported by a physician’s training grant from the National Institutes of Health T32 HL07066. Work was supported by NIH Program Project 4971265.