Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death

Semin Cancer Biol. 1993 Dec;4(6):327-32.


The maintenance of homeostasis in normal tissues reflects a balance between cell proliferation and cell death. The importance of both positive and negative regulators of cell growth has been well documented in neoplasia. Bcl-2 argues for the existence of a new category of oncogenes, regulators of cell death. The bcl-2 gene was identified at the chromosomal breakpoint of t(14; 18) bearing B cell lymphomas. Bcl-2 has proved to be unique among protooncogenes in blocking programmed cell death rather than promoting proliferation. In adults, bcl-2 is topographically restricted to progenitor cells and longlived cells but is much more widespread in the developing embryo. Transgenic mice that overexpress bcl-2 in the B cell lineage demonstrate extended cell survival, and progress to high grade lymphomas. Bcl-2 has been localized to mitochondria, endoplasmic reticulum and nuclear membranes, also the sites of reactive oxygen species generation. Bcl-2 does not appear to influence the generation of oxygen free radicals but does prevent oxidative damage to cellular constituents including lipid membranes. Bcl-2 deficient mice complete embryonic development and display relatively normal haematopoietic differentiation but undergo fulminant lymphoid apoptosis of thymus and spleen. Moreover, they demonstrate two potentially oxidation related pathologies: polycystic kidney disease and hair hypopigmentation. A family of bcl-2 related genes is emerging that includes Bax, a conserved homolog that heterodimerizes in vivo with bcl-2. A pre-set ratio of Bcl-2/Bax appears to determine the survival or death of cells following an apoptotic stimulus.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Transformation, Neoplastic / genetics
  • Chromosomes, Human, Pair 14 / ultrastructure
  • Chromosomes, Human, Pair 18 / ultrastructure
  • Gene Expression Regulation
  • Homeostasis
  • Humans
  • Lymphoma, Follicular / genetics
  • Mice
  • Mice, Transgenic
  • Oxidation-Reduction
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogenes*
  • Reactive Oxygen Species
  • Translocation, Genetic
  • bcl-2-Associated X Protein


  • BAX protein, human
  • Bax protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein