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 between different members of the Bcl-2 family that either promote or suppress apoptosis, The Bcl-2 homolog, Bak, promotes apoptosis and binds anti-apoptotic family members including Bcl-2 and Bcl-x(L). We have identified a domain in Bak that is both necessary and sufficient for cytotoxic activity and binding to Bcl-x(L). Sequences similar to this domain were identified in Bar and Bip1, two other proteins that promote apoptosis and interact with Bcl-x(L), and were likewise critical for their capacity to kill cells and bind Bcl-x(L). Thus, the domain is of central importance in mediating the function of multiple cell death-regulatory proteins that interact with Bcl-2 family members.