Farnesylated RhoB inhibits radiation-induced mitotic cell death and controls radiation-induced centrosome overduplication |
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Authors: | Milia J Teyssier F Dalenc F Ader I Delmas C Pradines A Lajoie-Mazenc I Baron R Bonnet J Cohen-Jonathan E Favre G Toulas C |
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Affiliation: | INSERM U563, CPTP, Département d'Innovation Thérapeutique et d'Oncologie Moléculaire, Institut Claudius Regaud, 20-24 rue du Pont St Pierre, 31052 Toulouse Cedex, France. |
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Abstract: | Our previous results demonstrated that expressing the GTPase ras homolog gene family, member B (RhoB) in radiosensitive NIH3T3 cells increases their survival following 2 Gy irradiation (SF2). We have first demonstrated here that RhoB expression inhibits radiation-induced mitotic cell death. RhoB is present in both a farnesylated and a geranylgeranylated form in vivo. By expressing RhoB mutants encoding for farnesylated (RhoB-F cells), geranylgeranylated or the CAAX deleted form of RhoB, we have then shown that only RhoB-F expression was able to increase the SF2 value by reducing the sensitivity of these cells to radiation-induced mitotic cell death. Moreover, RhoB-F cells showed an increased G2 arrest and an inhibition of centrosome overduplication following irradiation mediated by the Rho-kinase, strongly suggesting that RhoB-F may control centrosome overduplication during the G2 arrest after irradiation. Overall, our results for the first time clearly implicate farnesylated RhoB as a crucial protein in mediating cellular resistance to radiation-induced nonapoptotic cell death. |
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