Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death

Cell. 1993 Aug 27;74(4):609-19. doi: 10.1016/0092-8674(93)90509-o.

Abstract

Bcl-2 protein is able to repress a number of apoptotic death programs. To investigate the mechanism of Bcl-2's effect, we examined whether Bcl-2 interacted with other proteins. We identified an associated 21 kd protein partner, Bax, that has extensive amino acid homology with Bcl-2, focused within highly conserved domains I and II. Bax is encoded by six exons and demonstrates a complex pattern of alternative RNA splicing that predicts a 21 kd membrane (alpha) and two forms of cytosolic protein (beta and gamma). Bax homodimerizes and forms heterodimers with Bcl-2 in vivo. Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line. Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • Base Sequence
  • Blotting, Western
  • Cell Line
  • Cloning, Molecular
  • Conserved Sequence
  • Humans
  • Macromolecular Substances
  • Mice
  • Molecular Sequence Data
  • Polymerase Chain Reaction / methods
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / isolation & purification
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2
  • Restriction Mapping
  • Sequence Homology, Amino Acid
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • Bax protein, mouse
  • Macromolecular Substances
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein

Associated data

  • GENBANK/L22472
  • GENBANK/L22473
  • GENBANK/L22474
  • GENBANK/L22475
  • GENBANK/L33709
  • GENBANK/S60902
  • GENBANK/S60903
  • GENBANK/S60904
  • GENBANK/S60905
  • GENBANK/S60924