Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals

Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11318-23. doi: 10.1073/pnas.201208798.


BH3-only proteins function at a proximal point in a conserved cell death pathway by binding, through their BH3 domains, to other Bcl-2 family members and triggering mitochondrial events associated with apoptosis. Here, we describe a strongly pro-apoptotic BH3-only protein, designated Bbc3, whose expression increases in response to diverse apoptotic stimuli. bbc3 mRNA levels were induced by exposure to DNA-damaging agents and by wild-type p53, which mediates DNA damage-induced apoptosis. p53 transactivated bbc3 through consensus p53 binding sites within the bbc3 promoter region, indicating that bbc3 is a direct target of p53. Additionally, bbc3 mRNA was induced by p53-independent apoptotic stimuli, including dexamethasone treatment of thymocytes, and serum deprivation of tumor cells. Insulin-like growth factor-1 and epidermal growth factor, growth factors with broad anti-apoptotic activity, were each sufficient to suppress Bbc3 expression in serum-starved tumor cells. These results suggest that the transcriptional regulation of bbc3 contributes to the transduction of diverse cell death and survival signals.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins
  • Base Sequence
  • Binding Sites
  • Cell Death
  • Cell Survival
  • Cells, Cultured
  • Consensus Sequence
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Gene Expression Regulation / physiology*
  • Genes, p53
  • Humans
  • Leukemia, Myeloid
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Open Reading Frames
  • Polymerase Chain Reaction
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / metabolism
  • Proto-Oncogene Proteins*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Signal Transduction / physiology*
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*


  • Apoptosis Regulatory Proteins
  • BBC3 protein, human
  • Proteins
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53

Associated data

  • GENBANK/AF411827
  • GENBANK/U89287