Abstract
The role of the p53 protein (encoded by TP53) in tumour suppression relies partly on the ability of p53 to regulate the transcription of genes that are important in cell-cycle arrest and in apoptosis. But the apoptotic pathway mediated by p53 is not fully understood. Here we show that BID, a member of the pro-apoptotic Bcl-2 family of proteins, is regulated by p53. BID mRNA is increased in a p53-dependent manner in vitro and in vivo, with strong expression in the splenic red pulp and colonic epithelium of γ-irradiated mice. Both the human and the mouse BID genomic loci contain p53-binding DNA response elements that bind p53 and mediate p53-dependent transactivation of a reporter gene. In addition, BID-null mouse embryonic fibroblasts are more resistant than are wild-type fibroblasts to the DNA damaging agent adriamycin and the nucleotide analogue 5-fluorouracil, both of which stabilize endogenous p53. Our results indicate that BID is a p53-responsive 'chemosensitivity gene' that may enhance the cell death response to chemotherapy.
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Acknowledgements
We thank D. Dicker for assistance with flow cytometry. This work was supported by the Howard Hughes Medical Institute and by grants from the NIH.
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Figure S1. Additional EMSANI of both the human and mouse p53 binding elements. (PDF 252 kb)
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Sax, J., Fei, P., Murphy, M. et al. BID regulation by p53 contributes to chemosensitivity. Nat Cell Biol 4, 842–849 (2002). https://doi.org/10.1038/ncb866
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DOI: https://doi.org/10.1038/ncb866
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