The Role of Translational Regulation in Survival after Radiation Damage; an Opportunity for Proteomics Analysis.
In this review, we will summarize the data from different model systems that illustrate the need for proteome-wide analyses of the biological consequences of ionizing radiation (IR). IR remains one of three main therapy choices for oncology, the others being surgery and chemotherapy. Understanding how cells and tissues respond to IR is essential for improving therapeutic regimes against cancer. Numerous studies demonstrating the changes in the transcriptome following exposure to IR, in diverse systems, can be found in the scientific literature. However, the limitation of our knowledge is illustrated by the fact that the number of transcripts that change after IR exposure is approximately an order of magnitude lower than the number of transcripts that re-localize to or from ribosomes under similar conditions. Furthermore, changes in the post-translational modifications of proteins (phosphorylation, acetylation as well as degradation) are profoundly important for the cellular response to IR. These considerations make proteomics a highly suitable tool for mechanistic studies of the effect of IR. Strikingly such studies remain outnumbered by those utilizing proteomics for diagnostic purposes such as the identification of biomarkers for the outcome of radiation therapy. Here we will discuss the role of the ribosome and translational regulation in the survival and preservation of cells and tissues after exposure to ionizing radiation. In doing so we hope to provide a strong incentive for the study of proteome-wide changes following IR exposure.