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Protein Affects Radiation-Sensitive Programming and Cell Fate
Published: November 13, 2012
Posted: May 07, 2013

Understanding the potential effects of low doses of ionizing radiation on human health requires knowledge of how it influences biology at the tissue level. One key question is how irradiated cells communicate to their neighbors. Scientists at Pacific Northwest National Laboratory are working to define signaling pathways activated by low doses of radiation. They previously found that the protein annexin A2 is involved in the malignant transformation of cultured mouse epidermal cells by radiation. They now demonstrate that high and low doses of ionizing radiation increases A2 annexin levels in the nuclei of human and mouse monolayer cultures and in a human skin tissue model supporting a conserved nuclear function for annexin A2. Whole genome expression profiling in the presence and absence of annexin A2 identified altered transcriptional programming that changes the radioresponsive transcriptome. Bioinformatics predicted that silencing A2 may enhance cell death responses to stress associated with reduced activation of survival signals. The researchers validated the prediction by demonstrating that the A2-silenced cells were more likely to die after treatment with tumor necrosis factor alpha than control cells. Collectively, the data suggest that annexin A2 functions to regulate cell fate, which could impact the biological response to radiation. These results could lead to new targeted approaches in therapies directed at regulating radiation-induced cell death.

Reference: Waters, K. M., D. L. Stenoien, M. B. Sowa, C. H. Freiin Von Neubeck, W. B. Chrisler, R. Tan, R. L. Sontag, and T. J. Weber. 2013. "Annexin A2 Modulates Radiation-Sensitive Transcriptional Programming and Cell Fate," Radiation Research 179(1), 56-61. DOI: 10.1667/RR3056.1. (Reference link)

Contact: Noelle Metting, SC-23.2, (301) 903-8309
Topic Areas:

  • Research Area: Genomic Analysis and Systems Biology
  • Research Area: Computational Biology, Bioinformatics, Modeling
  • Legacy: Low Dose Radiation, Radiobiology

Division: SC-33.2 Biological Systems Science Division, BER


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