Farnesylated RhoB inhibits radiation-induced mitotic cell death and controls radiation-induced centrosome overduplication.
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.
Milia
J
J
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.
Teyssier
F
F
Dalenc
F
F
Ader
I
I
Delmas
C
C
Pradines
A
A
Lajoie-Mazenc
I
I
Baron
R
R
Bonnet
J
J
Cohen-Jonathan
E
E
Favre
G
G
Toulas
C
C
D000818:Animals; D016923:Cell Death / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D018385:Centrosome / Q000473:pathology* / Q000528:radiation effects*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D016195:G2 Phase / Q000528:radiation effects; D005720:Gamma Rays; D051379:Mice; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000528:radiation effects*; D041681:NIH 3T3 Cells; D020743:rhoB GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D005456:Fluorescent Dyes; D020743:rhoB GTP-Binding Protein; D016650:Fluorescein-5-isothiocyanate