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Ionizing radiation regulates expression of the c-jun protooncogene
M L Sherman1, R Datta, D E Hallahan
1Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Boston, MA.
Summary
Ionizing radiation exposure activates the c-jun protooncogene, a key gene in cellular signaling. This activation involves both transcriptional and posttranscriptional gene regulation, impacting cellular responses to radiation.
Area of Science:
- Molecular Biology
- Radiation Biology
- Genetics
Background:
- Gene expression regulation by ionizing radiation is poorly understood.
- Early response genes play critical roles in cellular signaling pathways.
Purpose of the Study:
- To investigate the effect of ionizing radiation on the expression of the c-jun protooncogene.
- To elucidate the regulatory mechanisms underlying c-jun gene induction by x-rays.
Main Methods:
- Northern blot analysis to quantify c-jun transcripts.
- Transcriptional run-on assays to assess gene transcription rates.
- Analysis of RNA half-life in the presence and absence of protein synthesis inhibitors.
Main Results:
- X-rays significantly increased c-jun gene expression in a time- and dose-dependent manner.
- Ionizing radiation was found to stimulate the rate of c-jun gene transcription.
- Posttranscriptional regulation, including prolonged RNA half-life, contributed to increased c-jun RNA levels.
- An inverse dose rate effect was observed, with lower dose rates leading to higher c-jun expression.
- Ionizing radiation also increased the expression of c-fos and jun-B transcripts.
Conclusions:
- Ionizing radiation induces c-jun protooncogene expression through both transcriptional activation and posttranscriptional mechanisms.
- The induction of early response genes like c-jun, c-fos, and jun-B by ionizing radiation may contribute to its pathophysiologic effects.