BH3-only proteins in cell death initiation, malignant disease and anticancer therapy

Cell Death Differ. 2006 Aug;13(8):1325-38. doi: 10.1038/sj.cdd.4401940. Epub 2006 Apr 28.


Induction of apoptosis in tumour cells, either by direct activation of the death receptor pathway using agonistic antibodies or recombinant ligands, or direct triggering of the Bcl-2-regulated intrinsic apoptosis pathway by small molecule drugs, carries high hopes to overcome the shortcomings of current anticancer therapies. The latter therapy concept builds on a more detailed understanding of how Bcl-2-like molecules maintain mitochondrial integrity and how BH3-only proteins and Bax/Bak-like molecules can undermine it. Means to unleash the apoptotic potential of BH3-only proteins in tumour cells, or bypass the need for BH3-only proteins by blocking possible interactions of Bcl-2-like prosurvival molecules with Bax and/or Bak allowing their direct activation, constitute interesting options for the design of novel anticancer therapies.

Publication types

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

MeSH terms

  • Animals
  • Cell Death
  • Cell Transformation, Neoplastic
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Proto-Oncogene Proteins c-bcl-2 / classification
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Tumor Suppressor Protein p53 / metabolism


  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53