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BID regulation by p53 contributes to chemosensitivity
Joanna K Sax1, Peiwen Fei, Maureen E Murphy
1Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Nature Cell Biology
|October 29, 2002
Summary
The p53 protein regulates the transcription of the BID gene, a key player in apoptosis. This discovery reveals BID as a chemosensitivity gene that may improve cancer treatment outcomes.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- The tumor suppressor protein p53 (encoded by TP53) regulates genes involved in cell-cycle arrest and apoptosis.
- The precise apoptotic pathway mediated by p53 remains incompletely understood.
Purpose of the Study:
- To investigate the regulation of the BID gene by p53.
- To elucidate the role of BID in p53-mediated apoptosis and chemosensitivity.
Main Methods:
- Analysis of BID mRNA expression in p53-dependent contexts.
- Identification and characterization of p53-binding DNA response elements in the BID genomic loci.
- Assessment of chemosensitivity in BID-null versus wild-type mouse embryonic fibroblasts.
Main Results:
- BID mRNA levels increase in a p53-dependent manner both in vitro and in vivo.
- p53 directly binds to response elements in the BID gene, mediating its transactivation.
- BID-null cells exhibit resistance to DNA-damaging agents like adriamycin and 5-fluorouracil, which stabilize p53.
Conclusions:
- BID is a direct transcriptional target of p53.
- BID acts as a p53-responsive 'chemosensitivity gene'.
- The p53-BID interaction enhances cellular responses to chemotherapy, potentially improving cancer treatment efficacy.