Background and Objectives. The apoptotic Bcl-2 family

y of death proteases, called caspases, that are activated in a proteolytic cascade to execute the cell death program. 1 The activation of upstream caspases represents a critical checkpoint in the decision of whether a cell will survive or die. 2 Upstream caspases are controlled by several molecules, including proteins of the Bcl-2 family. Some pro-apoptotic members of this family, such as Bik/Nbk, Blk, Bad, Bid, Bim and Hrk, contain only the BH3 cell death motif (BH3-only proteins) that acts as a dimerization domain for anti-apoptotic proteins (i.e., Bcl-2 and Bcl-xL). 3 The pro-apoptotic activity of these BH3-only proteins is mediated by the BH3 region, as deletion or mutation of this region abrogates their binding to Bcl-2 and Bcl-xL and their killing activity. 4 Furthermore, the BH3only proteins have been suggested to represent the physiologic antagonists of anti-apoptotic Bcl-2 family members. 5 We have previously shown that Hrk is specifically induced in murine myeloid