The Bcl-2 family
Several pathways leading to cell death converge on a family of pro-survival molecules known as the Bcl-2 family. These molecules play an important role in determining the fate of a cell and the interactions between them determines whether a cell lives or dies. The mechanisms by which Bcl-2 proteins regulate cell death are still being clarified, but a key interaction is the inhibition of the pro-survival activity of Bcl-2 family members by interaction with the death inducing BH3-only proteins. The over-expression of pro-survival proteins such as Bcl-2 (B cell lymphoma-2) and Mcl-1 (Myeloid cell leukaemia-1) in cancer has made these proteins the target of structure directed drug design to discover antagonists to their survival activity. To this end we have focused on structural characterization of these proteins and their complexes and have solved structures of Bcl-w and Mcl-1.
