Premature senescence, the induction of long term growth factor irreversible cell cycle arrest, is induced by the oxidative effects of reactive oxygen species and high level expression of certain oncogenes such as activated Ras. This arrest response is thought to be important for prevention of cellular transformation and carcinogenesis. Given that gene chip microarray studies indicate that CCNG2, the gene encoding the unconventional cyclin, cyclin G2, is upregulated upon oxidative stress and transient transfection with oncogenic RAS, we predict that cyclin G2 protein is upregulated by these cellular stresses. Furthermore, as CCNG2 is a direct transcriptional target of the forkhead box O (FOXO) family of transcription factors required for oxidative stress response induced cell cycle arrest, and ectopic expression of cyclin G2 induces withdrawal from the cell cycle, we hypothesize that cyclin G2 upregulation promotes the cell cycle arrest program of premature senescence. We are initiating investigations into the relationship between upregulated cyclin G2 expression and premature senescence. To further examine the cyclin G2 expression to cellular growth during senescence inducing stresses. Here we test whether cells transfected with oncogenic Ras elevate cyclin G2 protein expression at levels comparable to FOXO activation of cyclin G2. In addition we are examining the sub-cellular localization pattern of endogenous cyclin G2 induced by the two regulators, and the contribution of cyclin G2 to cell cycle control during premature senescence. Through these studies we seek to determine whether cyclin G2, as one of the gene products positively regulated by the FoxO1 and Foxo3 transcriptional activity, facilitates premature senescence programs.