BCL-2 proteins and apoptosis: Recent insights and unknowns

Biochem Biophys Res Commun. 2018 May 27;500(1):26-34. doi: 10.1016/j.bbrc.2017.06.190. Epub 2017 Jul 1.

Abstract

Proteins of the B-cell lymphoma-2 (BCL-2) family control the intrinsic apoptosis pathway. The pro-apoptotic BCL-2 proteins BAX and BAK can commit a cell to its programmed death by permeabilizing the outer mitochondrial membrane (OMM) and subsequent initiation of the caspase cascade. Therefore, the activities of BAX and BAK are precisely controlled by a complex network of proteins inside and outside the BCL-2 family. Cells survive by constant control of dynamic translocation and retrotranslocation of BAX and BAK to the mitochondria and back into the cytosol. Recent insights into BAX/BAK shuttling, BCL-2 protein interactions, the role of BH3-only proteins in apoptosis signaling and the active BAX complex set the stage for the development of novel strategies in cancer therapy and the analysis of cellular predisposition to apoptosis.

Keywords: BCL-2 proteins; BH3-only proteins; Mitochondrial apoptosis; Retrotranslocation.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / genetics
  • BH3 Interacting Domain Death Agonist Protein / genetics
  • BH3 Interacting Domain Death Agonist Protein / metabolism
  • Bcl-2-Like Protein 11 / genetics
  • Bcl-2-Like Protein 11 / metabolism
  • Caspases / genetics
  • Caspases / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Mitochondrial Membranes / metabolism
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protein Transport
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • bcl-2 Homologous Antagonist-Killer Protein / genetics*
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism
  • bcl-2-Associated X Protein / genetics*
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAK1 protein, human
  • BAX protein, human
  • BCL2 protein, human
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Bcl-2-Like Protein 11
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • Caspases