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

Biochem Biophys Res Commun. 2000 Feb 24;268(3):784-9. doi: 10.1006/bbrc.2000.2211.

Abstract

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 drugs 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Alkylation
  • Animals
  • Antineoplastic Agents, Alkylating / toxicity
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Apoptosis / radiation effects
  • DNA Damage
  • DNA Repair
  • DNA Replication / drug effects
  • DNA, Complementary / genetics
  • Methyl Methanesulfonate / toxicity
  • Mice
  • Rats
  • Transfection
  • Ultraviolet Rays
  • rhoB GTP-Binding Protein / genetics
  • rhoB GTP-Binding Protein / physiology*

Substances

  • Antineoplastic Agents, Alkylating
  • DNA, Complementary
  • Methyl Methanesulfonate
  • rhoB GTP-Binding Protein