c-Rel arrests the proliferation of HeLa cells and affects critical regulators of the G(1)/S-phase transition

A tetracycline-regulated system was used to characterize the effects of c-Rel on sell proliferation, The expression of c-Rd in HeLa cells led to growth arrest at the G(1)/S-phase transition, which correlated with its nuclear localization and the induction of endogenous I kappa B alpha expression. These changes were accompanied by a decrease in E2F DNA binding and the accumulation of the hypophosphorylated form of Rb. In vitro kinase assays showed a reduction ire Cdk2 kinase activity that correlated with elevated levels of p21(WAF1) Cdk inhibitor and p53 tumor suppressor protein, While the steady-state levels of WAF1 transcripts were increased, pulse-chase analysis revealed a sharp increase in p53 protein stability. Importantly, the deletion of the C-terminal transactivation domains of c-Rel abolished these effects. Together, these studies demonstrate that c-Rel fan affect cell cycle control and suggest the involvement of the p21(WAF1) and p53 cell cycle regulators.