Role of Bcl‐2 family of proteins in malignancy

Abstract

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.