Ras-related GTPase RhoB forces alkylation-induced apoptotic cell death

rhoB encoding a Ras-related GTPase is immediate; early inducible by genotox ic treatments. To address the question of the physiological role of RhoB in cellular defense, cells stably overexpressing wild-type RhoB protein were generated. Overexpression of RhoB renders cells hypersensitive to the killi ng effect of alkylating agents including antineoplastic drags but not to UV -light and doxorubicin. As compared to control cells, RhoB overexpressing c ells revealed an increase in the frequency of alkylation-induced apoptotic cell death. This indicates that RhoB is involved in modulating apoptotic si gnaling. Furthermore, overexpression of RhoB resulted in a prolonged transi ent block to DNA replication upon MMS treatment. UV-induced replication blo ckage was not affected by RhoB. Based on the data we suggest RhoB to be a n ovel regulatory factor which takes influence on the level of cytotoxicity o f DNA damaging drugs and forces cells to alkylation-induced apoptosis. The data indicate that this might be due to RhoB mediated delay in cell cycle p rogression upon alkylation-treatment. (C) 2000 Academic Press.