Cdc42, but not RhoA, regulates cyclin D1 expression in bovine tracheal myocytes

We previously demonstrated that Rac1 increased cyclin D1 promoter activity in an extracellular signal-regulated kinase (ERK)-independent, antioxidant- sensitive manner. Here, we examined the regulation of cyclin D1 expression by Cdc42 and RhoA. Overexpression of active Cdc42, but not of RhoA, induced transcription from the cyclin D1 promoter. Furthermore, dominant negative Cdc42, but not RhoA, attenuated platelet-derived growth factor-mediated act ivation of the cyclin D1 promoter. Overexpression of active Cdc42 increased cyclin D1 protein abundance in COS cells. Cdc42-induced cyclin D1 promoter activation was independent of ERK as evidenced by insensitivity to PD-9805 9, an inhibitor of mitogen-activated protein kinase/ERK kinase (MEK). Furth ermore, Cdc42 was neither sufficient nor required for activation of ERK. Si milar to Rac1-induced cyclin D1 expression, pretreatment with the antioxida nts catalase and ebselen inhibited Cdc42-mediated transcription from the cy clin D1 promoter. Finally, like Rac1, active Cdc42 induced transactivation of the cyclin D1 promoter cAMP response element binding protein/activating transcription factor-2 binding site. Together, these data suggest that in a irway smooth muscle cells, Cdc42 and Rac1 share a common signaling pathway to cyclin D1 promoter activation.