Death and survival are two opposite fates of cells that ironically are often played out by the same molecular machinery. The Bcl-2 family plays central roles in the regulation of apoptotic pathways, and is a classical example of the intertwining of death and survival mechanisms.  The Bcl-2 machinery consists of both pro-apoptotic and anti-apoptotic (pro-survival) family members:

    1.  Pro-apoptotic:
         a. BH3-only: BAD, Bid, Bik, Bim, Bmf, Hrk, Noxa, Puma
         b. Multidomain: BAK, BAX, BOK, Bcl-XS
    2.  Pro-survival: A1, Bcl-2, Bcl-XL, Mcl-1

The BH3-only proteins are thought to be integrators of diverse stress signals.  They are normally present at low levels or in an inactive state, and undergo activating transcriptional induction or post-translational modifications in response to various stress stimuli (Figure 1). For example Noxa and Puma are transcribed following DNA damage-p53 induction, whereas Bid is cleaved following death receptor engagement.  Active BH3-only pro-apoptotic proteins translocate from the cytoplasm to the mitochondria where they interfere with the function of pro-survival family members, thereby activating down-stream apoptotic signaling events.