Bcl-2 mutants with restricted subcellular location reveal spatially distinct pathways for apoptosis in different cell types

EMBO J. 1996 Aug 15;15(16):4130-41.


Human Bcl-2 is located in multiple intracellular membranes when expressed in MDCK and Rat-1/myc cells. We restricted expression to the endoplasmic reticulum or mitochondria by exchanging the Bcl-2 carboxy-terminal insertion sequence for an equivalent sequence from cytochrome b5 or ActA, respectively. MDCK cells are protected from serum deprivation-induced apoptosis by both wild-type Bcl-2 and the mutant targeted to mitochondria but not by the mutant targeted to endoplasmic reticulum. In contrast, when expressed in Rat-1/myc cells, the Bcl-2 mutant located at the endoplasmic reticulum is more effective than that targeted to mitochondria. In MDCK cells both mutants bind Bax as effectively as wild-type, demonstrating that Bax binding is not sufficient to prevent apoptosis.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / physiology*
  • Cell Line
  • Dogs
  • Endoplasmic Reticulum / metabolism
  • Epithelium / metabolism
  • Fibroblasts / metabolism
  • Humans
  • Intracellular Membranes / metabolism*
  • Kidney / cytology
  • Mice
  • Mitochondria / metabolism
  • Molecular Sequence Data
  • Organ Specificity
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • bcl-2-Associated X Protein


  • BAX protein, human
  • Bax protein, mouse
  • Bax protein, rat
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • Recombinant Fusion Proteins
  • bcl-2-Associated X Protein