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PMID:11572983
| Citation |
Han, J, Flemington, C, Houghton, AB, Gu, Z, Zambetti, GP, Lutz, RJ, Zhu, L and Chittenden, T (2001) 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. 98:11318-23 |
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| Abstract |
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. |
| Links |
PubMed PMC58727 Online version:10.1073/pnas.201208798 |
| Keywords |
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 |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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