title: Overexpression of wild-type RhoA produces growth arrest by disrupting actin cytoskeleton and microtubules.
abstract: We have investigated the role of Rho GTPase in cell growth by generating stable cells that express the wild-type RhoA (RhoA(wt)) under the control of an inducible promoter. Induction of RhoA(wt) had a biphasic effect on the actin cytoskeleton. At low levels of expression, RhoA(wt) stimulated the assembly of actin stress fibers without affecting cell growth. At high levels, there was a paradoxical disruption of the actin cytoskeleton accompanied by a growth arrest. Cell cycle analysis revealed a dual block at the G(1)/S and G(2)/M checkpoints. The G(1)/S arrest correlated with the accumulation of p21(Cip1), resulting in the inhibition of cdk2 activity, whereas the G(2)/M block correlated with the loss of microtubules. The cyclin B level and the cdc2 kinase activity, however, were increased, suggesting that the progression through mitosis rather than entry into the G(2)/M is defective when RhoA(wt) is overexpressed. Similar cell cycle defects and the loss of microtubules were observed after a cytochalasin D treatment, indicating that the ability of RhoA to regulate the integrity of actin cytoskeleton may be critical for the cell cycle transition through both the G(1)/S and M phase checkpoints.
authors.affiliation: Department of Medicine, Microbiology, Immunology, and Molecular Genetics, and Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California 90095, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.forename: C
authors.initials: C
authors.lastname: Wong
authors.forename: D D
authors.initials: DD
authors.lastname: Chang
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002453:Cell Cycle; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism*; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D008870:Microtubules / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D017931:DNA Primers; D020742:rhoA GTP-Binding Protein