IMPORTANCE OF THE BCL-2 FAMILY IN CELL-DEATH REGULATION

Bcl-2 was first identified as a novel transcript associated with the t (14;18) chromosomal breakpoint which occurs in most follicular lymphom as. The deregulated expression of bcl-2 was found to contribute to mul tistep neoplasia through the suppression of cell death, or apoptosis, in transgenic mouse models. Bcl-2 was subsequently shown to be normall y expressed in a variety of tissues and to significantly inhibit the i nduction of apoptosis in many experimental systems. Bcl-2 is now known to be structurally similar to other proteins, in particular within th e domains referred to as BH1 and BH2. This multigene family of cell de ath regulators includes members which enhance rates of apoptosis, incl uding bcl-x(S) and bar, and those which inhibit apoptosis, including M CL-1 and bcl-x(L). Members of the bcl-2 family physically interact wit h other proteins, including other family members and these interaction s appear to modulate their function. The mechanism(s) by which bcl-2 f amily members regulate cell death remain in large part unknown, althou gh recent evidence suggests that bcl-2 may interfere with cellular sig nalling events involved in apoptosis induction.