The BCL ‐2 Family Proteins – Key Regulators and Effectors of Apoptosis

Abstract

BCL‐2 was the first cloned component of the mechanism for apoptosis – the process by which metazoan cells commit suicide – to be recognized. Mammals are now known to carry genes for a large number of BCL‐2 like proteins, some of which, like BCL‐2 itself, inhibit apoptosis, and others that promote or are required for apoptosis. Direct interactions between BCL‐2 family members are essential for the proper regulation and implementation of apoptosis during development and for homoeostasis. Abnormalities to the regulation of cell death, such as those caused by mutations to genes for BCL‐2 family members prevent apoptosis occurring when it should, and can lead to diseases including cancer. Understanding the roles of BCL‐2 family members, their structures and how they interact, has allowed the development of novel agents for the treatment of cancer that are now in clinical trials. Key concepts A major mechanism by which mammalian cells kill themselves involves members of the BCL‐2 family of proteins, some of which promote cell death, and others which inhibit cell death. BCL‐2 family proteins interact with each other to regulate and implement the cell death programme. Abnormalities to the regulation of this cell death process, including mutations to genes for BCL‐2 family members, can lead to a disease, such as cancer.