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  • Title: Farnesylated RhoB prevents cell cycle arrest and actin cytoskeleton disruption caused by the geranylgeranyltransferase I inhibitor GGTI-298.
    Author: Allal C, Pradines A, Hamilton AD, Sebti SM, Favre G.
    Journal: Cell Cycle; 2002; 1(6):430-7. PubMed ID: 12548020.
    Abstract:
    Here we demonstrate that the geranylgeranyltransferase-I inhibitor GGTI-298 inhibits the RhoB pathway and disrupts stress fiber and focal adhesion formation in NIH-3T3 cells. Farnesylated (V14)RhoB-CAIM (resistant to GGTI-298), but not geranylgeranylated (V14)RhoB (-CLLL), prevented inhibition of actin stress fiber and focal adhesion formation, underlining the critical role of RhoB. In contrast, farnesylated, (V14)RhoA (-CVLS) was unable to prevent effects of GGTI 298 on cytoskeleton organization. Furthermore, the ability of GGTI-298 to induce p21(WAF) and to block cells in the G(0)/G(1) phase of the cell cycle was also prevented by farnesylated (V14)RhoB but not by farnesylated (V14)RhoA. Moreover, treatment with GGTI-298 of cells expressing farnesylated RhoB results in accumulation of these cells in the G(2)/M phase. Therefore, the RhoB pathway is a critical target of GGTI-298.
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