Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 268, Issue 3, Pages 784-789Publisher
ACADEMIC PRESS INC
DOI: 10.1006/bbrc.2000.2211
Keywords
small GTPases; Rho; drug resistance; apoptosis
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rhoB encoding a Ras-related GTPase is immediate; early inducible by genotoxic 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 killing effect of alkylating agents including antineoplastic drags but not to UV-light and doxorubicin. As compared to control cells, RhoB overexpressing cells revealed an increase in the frequency of alkylation-induced apoptotic cell death. This indicates that RhoB is involved in modulating apoptotic signaling. Furthermore, overexpression of RhoB resulted in a prolonged transient block to DNA replication upon MMS treatment. UV-induced replication blockage was not affected by RhoB. Based on the data we suggest RhoB to be a novel regulatory factor which takes influence on the level of cytotoxicity of 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 progression upon alkylation-treatment. (C) 2000 Academic Press.
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