Role of Oxidative Stress-Induced Protein Arginylation in Radiation Response
Abstract
Ionizing radiation is commonly used to treat aggressive types of prostate cancer. While successful outcomes are observed in some patients, a high failure rate (up to 40%) is also reported. Currently, no biomarker exists to predict (or explain) the various outcomes, making it difficult to decide treatment options. Oxidative damage in the cells, caused by ionizing radiation, is the direct cause of cellular damage and death. In response to oxidative stress, the cell often induces arginylation, a post-translational addition of an extra arginine to the N-terminus of a protein/peptide. It is known to induce degradation of the modified proteins, and, in some cases, induces functional modification of the proteins. It is reported that arginylation preferentially takes places on oxidized or nitrosylated proteins, which are often generated during radiation. Furthermore, arginylation also affects protein fragments, which commonly result from radiation damage. All this evidence indicates arginylation might be relevant to ionizing radiation. However, arginylation is still a poorly understood process and most relevant studies are in the nascent stage. Consequentially, there is nearly nothing known about the role of arginylation in response to radiation, and there has not been any documented attempt to study arginylation from this perspective. In this study, we will test whether arginylation helps the cells to survive radiation damage. Furthermore, we will test whether the level of the enzyme that performs arginylation (arginyltransferase 1; Ate1) is associated with the outcome of radiotherapy in prostate cancer patients. If we find the results we anticipate, this study will provide a breakthrough in our understanding of the clinical decisions regarding radiotherapy for prostate cancers. Our research is therefore relevant to this Prostate Cancer Research Program overarching challenge: "Distinguish aggressive from indolent disease in men newly diagnosed with prostate cancer." Also, our research falls into these focus areas: "Biomarker Development" and "Genetics."
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510329
Entities
People
- Fangliang Zhang
Organizations
- United States Army
- University of Miami