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

Nat Rev Mol Cell Biol. 2014 Jan;15(1):49-63. doi: 10.1038/nrm3722.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins / chemistry
  • Apoptosis Regulatory Proteins / physiology
  • Apoptosis*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Protein Multimerization
  • Protein Structure, Secondary
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Signal Transduction

Substances

  • Apoptosis Regulatory Proteins
  • Proto-Oncogene Proteins c-bcl-2