Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy

PE Czabotar, G Lessene, A Strasser… - Nature reviews Molecular …, 2014 - nature.com
Nature reviews Molecular cell biology, 2014nature.com
The BCL-2 protein family determines the commitment of cells to apoptosis, an ancient cell
suicide programme that is essential for development, tissue homeostasis and immunity. Too
little apoptosis can promote cancer and autoimmune diseases; too much apoptosis can
augment ischaemic conditions and drive neurodegeneration. We discuss the biochemical,
structural and genetic studies that have clarified how the interplay between members of the
BCL-2 family on mitochondria sets the apoptotic threshold. These mechanistic insights into …
Abstract
The BCL-2 protein family determines the commitment of cells to apoptosis, an ancient cell suicide programme that is essential for development, tissue homeostasis and immunity. Too little apoptosis can promote cancer and autoimmune diseases; too much apoptosis can augment ischaemic conditions and drive neurodegeneration. We discuss the biochemical, structural and genetic studies that have clarified how the interplay between members of the BCL-2 family on mitochondria sets the apoptotic threshold. These mechanistic insights into the functions of the BCL-2 family are illuminating the physiological control of apoptosis, the pathological consequences of its dysregulation and the promising search for novel cancer therapies that target the BCL-2 family.
nature.com