Article abstract
Nature Cell Biology 4, 842 - 849 (2002)
Published online: 28 October 2002 | doi:10.1038/ncb866
BID regulation by p53 contributes to chemosensitivity
Joanna K. Sax1, Peiwen Fei1, Maureen E. Murphy2, Eric Bernhard3, Stanley J. Korsmeyer4 & Wafik S. El-Deiry1
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 
-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.
- Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Departments of Medicine, Pharmacology, and Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
- Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
- Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
- Howard Hughes Medical Institute, Departments of Pathology and Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Correspondence to: Wafik S. El-Deiry1 e-mail: wafik@mail.med.upenn.edu
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