Role Of RhoB In Cellular Oxidative Stress

For majority of aerobic organisms,aerobic metabolism within the cell is fundamental to life activities.About 2%of oxygen in an organism will become reactive oxygen species(ROS)during cellular aerobic metabolism.Since ROS carry strong oxidative activity,abnormal increase of ROS concentration will trigger oxidative stress to the organism,therefore cause oxidative damage by excessive modification of biological macromolecules,leading to cell dysfunction and even cell death.It has been demonstrated that ROS levels are significantly higher in a variety of cancer cells than in normal cells,and tumor cells express higher levels of oxidized proteins in order to maintain their own redox balance and reestablish a redox balance system different from that of normal cells,suggesting that ROS may be a target for cancer therapy.As a member of the Rho family of small GTPases,RhoB has been shown to play an integral role in mediating cell death following ionizing radiation or other DNA damaging agents in Ras transformed cell lines,Nevertheless,the role of RhoB in the regulation of cellular ROS stress is poorly studied.In this study we used H2O2 to increase oxidative stress in cells and found that protein level of RhoB was increased in response to H2O2 treatment.Meanwhile,the sumoylation of RhoB was also increased by H2O2 treatment.Moreover,we found that knockout of RhoB significantly prevented H2O2 treatment-induced cancer cell death,whereas it did not affect the cell cycle and ROS levels.Interestingly,treatment of H2O2 remarkably caused translocation of RhoB from plasma membrane to lysosomes,suggesting that RhoB might promotes autophagy to induce cell death in response to ROS stress.Furthermore,we found that RhoB protein levels in colorectal tumor tissues were significantly lower than the surrounding normal tissues.Meanwhile,by analyzing public data,we found that RhoB expression level is frequently downregulated in various types of cancer,and is positively correlated with the survival rate of the patients.Hence,our study demonstrates a potential role of RhoB in regulating ROS stress response and tumor development,providing new clues to manipulate ROS in cancer therapy.