A CONSERVED DOMAIN IN BAK, DISTINCT FROM BH1 AND BH2, MEDIATES CELL-DEATH AND PROTEIN-BINDING FUNCTIONS

Regulation of the cell death program involves physical interactions be tween different members of the Bcl-2 family that either promote or sup press apoptosis, The Bcl-2 homolog, Bak, promotes apoptosis and binds anti-apoptotic family members including Bcl-2 and Bcl-x(L). We have id entified a domain in Bak that is both necessary and sufficient for cyt otoxic activity and binding to Bcl-x(L). Sequences similar to this dom ain were identified in Bar and Bip1, two other proteins that promote a poptosis and interact with Bcl-x(L), and were likewise critical for th eir capacity to kill cells and bind Bcl-x(L). Thus, the domain is of c entral importance in mediating the function of multiple cell death-reg ulatory proteins that interact with Bcl-2 family members.