Bcl-2 family proteins as therapeutic targets.
The mitochondrion provides the stage for the interplay of molecular interactions that regulate apoptosis via the intrinsic pathway. The release of apoptogenic factors from this compartment constitutes a critical juncture in this apoptotic pathway. Regulation of the integrity of the outer mitochondrial membrane (OMM) is the task of the Bcl-2 family of proteins. A network of interactions between the various subgroups of the family decides the apoptotic fate of a cell and, as such, an imbalance within this network can lead to a variety of disease states. In particular, over-expression of pro-survival Bcl-2 family proteins is a hallmark of many cancers. Here we discuss recent advances in targeting the Bcl-2 family with both peptides and small molecules.
Czabotar
Peter E
PE
The Walter and Eliza Hall Institute for Medical Research, 1G Royal Parade, Parkville, Victoria, Australia. czabotar@wehi.edu.au
Lessene
Guillaume
G
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects* / Q000502:physiology; D054852:Small Molecule Libraries / Q000494:pharmacology
D000970:Antineoplastic Agents; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D054852:Small Molecule Libraries