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BTG gene expression in the p53-dependent and -independent cellular response to DNA damage
U Cortes1, C Moyret-Lalle, N Falette
1INSERM U453 and Unité d'Oncologie Moléculaire, Centre Léon Bérard, Lyon, France.
Abstract:
Exposure of mammalian cells to genotoxic agents evokes a complex cellular response. An ordered series of molecular events is necessary to sense DNA damage, transduce the signal, and ultimately delay the cell cycle or trigger apoptosis. Recently, we have shown that BTG2/TIS21 gene expression was induced in response to DNA damage through a p53-dependent pathway. This gene belongs to a newly identified family of structurally related genes whose other known human members are BTG1, BTG3, and Tob. To define the respective involvement of these four related genes in the cellular response to DNA damage, we studied their expression in human cell lines after a variety of genotoxic treatments. Our results demonstrated that were BTG1, BTG2/TIS21, and Tob genes the DNA damage--inducible genes. However, BTG2/TIS21 appeared to be the only p53-transcriptional target gene. We speculate that BTG proteins may play a coordinate role in a general transduction pathway that is induced in response to DNA damage. It has been previously described that recombinant BTG1 and BTG2/TIS21 can physically interact with PRMT1, an arginine methyl transferase, suggesting that BTG1 and BTG2/TIS21 induction may lead to posttranslational modifications of cellular proteins. In support of this hypothesis, we showed that the endogenous induction of BTG1 and BTG2 after genotoxic treatment was correlated with a modulation of protein methylation.
Insights
The BTG1, BTG2/TIS21, and Tob genes are induced by DNA damage. BTG2/TIS21 is a p53 target, and these proteins may regulate cellular responses via protein methylation.
Area of Science:
- Molecular Biology
- Cellular Biology
- Genetics
Background:
- Genotoxic agents trigger complex cellular responses involving DNA damage sensing, signal transduction, cell cycle arrest, or apoptosis.
- The BTG2/TIS21 gene is induced by DNA damage via a p53-dependent pathway.
- The BTG gene family includes BTG1, BTG2/TIS21, BTG3, and Tob, with potential roles in cellular responses.
Purpose of the Study:
- To investigate the involvement of BTG1, BTG2/TIS21, BTG3, and Tob genes in the cellular response to DNA damage.
- To determine which of these genes are DNA damage-inducible and their relationship with the p53 pathway.
- To explore the potential role of BTG proteins in posttranslational modifications following DNA damage.
Main Methods:
- Studying the expression of BTG1, BTG2/TIS21, BTG3, and Tob genes in human cell lines.
- Utilizing various genotoxic treatments to induce DNA damage.
- Analyzing gene expression patterns and protein methylation levels.
Main Results:
- BTG1, BTG2/TIS21, and Tob genes were found to be inducible by DNA damage.
- BTG2/TIS21 was identified as the sole p53-transcriptional target gene among those studied.
- Genotoxic treatment induced BTG1 and BTG2 expression, correlating with modulated protein methylation.
Conclusions:
- BTG1, BTG2/TIS21, and Tob are DNA damage-inducible genes, with BTG2/TIS21 being a p53 target.
- BTG proteins may participate in a coordinated pathway for DNA damage response.
- The induction of BTG1 and BTG2 following genotoxic stress is linked to alterations in protein methylation.