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WW domain-containing FBP-30 is regulated by p53
1Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Case 906, 13288 Marseille Cedex 9, France.
Cell Death and Differentiation
|October 8, 1999
Summary
This study identifies FBP-30 as a gene upregulated in thymocytes during programmed cell death. Its expression is p53-dependent and linked to cell death, suggesting indirect p53 regulation.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- Programmed cell death, or apoptosis, is crucial in T cell development.
- Gamma-irradiation induces apoptosis in thymocytes.
- Identifying genes involved in radiation-induced apoptosis is important for understanding T cell regulation.
Purpose of the Study:
- To identify genes transcriptionally upregulated in thymocytes undergoing apoptosis after gamma-irradiation.
- To characterize the function and regulation of a novel gene, FBP-30, identified in this process.
Main Methods:
- Subtractive cloning to identify upregulated genes.
- cDNA sequencing to analyze gene conservation.
- p53-dependent gene expression analysis in wild-type and p53-deficient thymocytes.
- Analysis of FBP-30 expression in response to a temperature-sensitive p53 mutant.
- Investigation of FBP-30 regulation using protein synthesis inhibitors.
Main Results:
- Approximately 60 genes were found to be upregulated during thymocyte apoptosis.
- FBP-30, encoding a WW domain, was identified and found to be conserved across mammals.
- FBP-30 expression is primarily in T cells and is upregulated by gamma-irradiation in a p53-dependent manner.
- FBP-30 induction kinetics are rapid and occur even with protein synthesis inhibitors, indicating indirect p53 regulation via a labile inhibitor.
Conclusions:
- FBP-30 is a novel gene upregulated during p53-mediated thymocyte apoptosis.
- p53 directly or indirectly regulates FBP-30 expression, which correlates with cell death.
- FBP-30 regulation involves the downregulation of a labile inhibitor by p53.