BCL-2 HETERODIMERIZES IN-VIVO WITH A CONSERVED HOMOLOG, BAX, THAT ACCELERATES PROGRAMMED CELL-DEATH

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 B cl-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 b y six exons and demonstrates a complex pattern of alternative RNA spli cing that predicts a 21 kd membrane (alpha) and two forms of cytosolic protein (beta and gamma). Bax homodimerizes and forms heterodimers wi th Bcl-2 in vivo. Overexpressed Bax accelerates apoptotic death induce d by cytokine deprivation in an IL-3-dependent cell line. Overexpresse d 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.