Bcl-2 Gene Family

The Bcl-2 family of cytoplasmic proteins are major regulators of programmed cell death. This process of cellular suicide, termed apoptosis, is thought to be conserved among all multicellular organisms. Apoptosis is vital for normal development, maintenance of tissue homeostasis, and proper immune function; disturbances in it are implicated in many disorders including cancer, degenerative diseases, and autoimmune disorders. Members of the Bcl-2 family, some of which work in opposition to the others, determine whether a cell undergoes apoptosis. The process of apoptosis is ultimately carried out by proteases of the caspase group, which cleave vital cellular proteins. However, the caspases are normally maintained as inactive precursors. Thus, the Bcl-2 family, in response to developmental and environmental cues and various intracellular damage signals, determines whether certain pro-caspases are activated in order to initiate the proteolytic cascade that causes cell death. Mutations in the BCL2 gene are seen in several different types of cancer. Mutations that deregulate apoptosis may also render cancer cells resistant to therapy. Knowledge of the intricacies of the BCL2-regulated apoptosis pathway has led scientists to create novel chemotherapeutic agents targeting the Bcl-2 family of proteins to facilitate tumor cell destruction.