The Emerging Roles of the Ubiquitination/deubiquitination System in Tumor Radioresistance regarding DNA damage responses, cell cycle regulation, hypoxic responses, and antioxidant properties: Insight into the Development of Novel Radiosensitizing Strategies

Publication date: Available online 22 July 2017 Source:Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis Author(s): Yoko Goto, Sho Kpyasu, Minoru Kobayashi, Hiroshi Harada Radiation therapy is one of the first-line treatments for many cancers, with no less than half of cancer patients receiving it in the US. Despite the development of innovative and high-precision radiation therapy strategies, many patients still experience local tumor recurrence after the treatment, at least in part, due to the existence of radioresistant cells in malignant tumor tissues. Among the various biological processes known to induce radioresistance, a post-translational protein modification, ubiquitination, has received marked attention in recent years. Ubiquitination, in which highly conserved ubiquitin polypeptides are covalently attached to their target proteins, has long been recognized as a system to tag unnecessary proteins for 26S proteasome-dependent proteolysis. However, accumulating lines of evidence recently revealed that it acts as a signal molecule in diverse biological processes as well, and its functional disorder was found to cause not only tumor development and various diseases but also tumor radioresistance. The present review summarizes the latest knowledge about how the cancer-related disorder of the ubiquitination systems induces the radioresistance of cancer cells by influencing intrinsic pathways, each of which potentially affects the radioresistance...
Source: Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis - Category: Cytology Source Type: research