Disruption of the Actin Cytoskeleton Leads to Inhibition of Mitogen-Induced Cyclin E Expression, Cdk2 Phosphorylation, and Nuclear Accumulation of the Retinoblastoma Protein-Related p107 Protein

Stability of p21Waf1/Cip1 CDK inhibitor protein is responsive to RhoA-mediated regulation of the actin cytoskeleton

“…These results, therefore, have significant implications for targeting strategies for cancer chemotherapy. An intact actin cytoskeleton and normal Rho signalling are associated with cell proliferation, whereas Rho inhibition and loss of cytoskeletal integrity are associated with cell-cycle arrest (Olson et al, 1995;Bohmer et al, 1996;Assoian and Zhu, 1997;Olson et al, 1998;Reshetnikova et al, 2000;Sahai et al, 2001;Huang and Ingber, 2002). Although the mechanism by which Factin influences p21 levels has not been extensively studied, the growth arrest of adherent cells placed in suspension has been associated with actin disruption and high p21 levels (Fang et al, 1996;Zhu et al, 1996;Bottazzi et al, 1999).…”

Cytoskeletal Organization and Rb Tumor Suppressor Gene

“…The essence of actin cytoskeleton for G1 phase progression, however, is dependent on the stage of G1 phase. For instance, accumulated literatures have shown that intact actin cytoskeleton was required for mid to late G1 phase progression (116)(117)(118)(119)(120). Also, serum stimulation and cell anchorage may also be involved in the G1 phase progression (121).…”

“…It is reasonable that disruption of actin filaments would lead to a G1 phase arrest. Indeed, exposure of cultured cells to sublethal concentration of actin inhibitors, such as cytochalasin or latrunculin, cause actin cytoskeletal destabilization and G1 phase arrest (117)(118)(119)122). In some cases, cells were synchronized to G1 phase using lovastatin (118) or serum-starvation (117) before cytochalasin treatment to avoid the interference of results from cells in other phases of cell cycle.…”

Signal Transduction and Actin in the Regulation of G1-Phase Progression

“…Indeed, disruption of actin architecture with pharmacological agents leads to G1 arrest in a variety of cell types. [134][135][136][137][138][139][140][141][142][143][144][145] Although cytoskeleton-dependent G1 arrest is related to inhibition of cyclin E expression in Swiss 3T3 cells, 142 most studies report a failure to induce sustained activity of the p42/p44 MAPKs, expression of cyclin D1, and downregulation of the cdk inhibitor p27 KIP1 . [138][139][140][141]144 In contrast to the cell-cycle block obtained with pharmacological inhibitors of actin polymerization, inhibition of the Rho-Rho kinase (ROCK) pathway required for stress fiber formation does not prevent the induction of cyclin D1-and G1-phase progression.…”