Role of Bcl-2 family of proteins in malignancy.

B cell lymphoma gene-2 (Bcl-2) is the prototypic member of a growing family of proteins that play evolutionarily conserved, key regulatory roles in apoptosis. The Bcl-2 family members are characterized by the presence of one or more Bcl-2 homology domains and are comprised of both the prosurvival and proapoptotic proteins. Bcl-2 itself is a prosurvival member of the family and its aberrant expression has been linked to a variety of different cancers, including several hematological malignancies. Although the exact mechanism of action of Bcl-2 family of proteins in regulating apoptosis is still a matter of some debate, these proteins appear to act upstream of caspase activation. Many recent studies have shown the therapeutic potential of targeting Bcl-2 family members for the treatment of cancer. This article summarizes what is currently known about Bcl-2-like proteins and how the evolving understanding of the biology of these proteins is paving way for the development of novel cancer therapeutics. Copyright 2001 John Wiley & Sons, Ltd.