RhoA prenylation is required for promotion of cell growth and transformation and cytoskeleton organization but not for induction of serum response element transcription

The importance of post-translational geranylgeranylation of the GTPase RhoA for its ability to induce cellular proliferation and malignant transformat ion is not well understood. In this manuscript we demonstrate that geranylg eranylation is required for the proper cellular localization of V14RhoA and for its ability to induce actin stress fiber and focal adhesion formation. Furthermore, V14RhoA geranylgeranylation was also required for suppressing p21(WAF) transcription, promoting cell cycle progression and cellular prol iferation. The ability of V14RhoA to induce focus formation and enhance pla ting efficiency and oncogenic Ras anchorage-dependent growth was also depen dent on its geranylgeranylation. The only biological activity of V14RhoA th at was not dependent on its prenylation was its ability to induce serum res ponse element transcriptional activity. Furthermore, we demonstrate that a farnesylated form of V14RhoA was also able to bind RhoGDI-1, was able to in duce cytoskeleton organization, proliferation, and transformation, and was just as potent as geranylgeranylated V14RhoA at suppressing p21(WAF) transc riptional activity. These results demonstrate that RhoA geranylgeranylation is required for its biological activity and that the nature of the lipid m odification is not critical.