Ras-related GTPase RhoB represses NF-kappa B signaling

rhoB encoding a Ras-related GTPase is immediate-early inducible by genotoxi c treatments, indicating that it is part of the cellular stress response. H ere, we investigated the influence of RhoB on signal pathways that are rapi dly evoked by genotoxic compounds. The data obtained show that wild-type Rh oB neither affects activation of mitogen-activated protein kinases nor AP-1 -dependent gene expression. However, RhoB inhibited both basal and genotoxi c agent-stimulated activity of the transcription factor nuclear factor KB ( NF-kappaB), Thus, RhoB attenuated alkylation-induced increase in the DNA bi nding activity of NF-kappaB and abrogated NF-kappaB-driven gene expression. Furthermore, RhoB inhibited decrease in the cellular amount of I kappaB al pha after genotoxic stress as well as after tumor necrosis factor a and 12- O-tetradecanoylphorbol acetate treatment. This indicates that RhoB represse s NF-kappaB activation by inhibiting dissociation and subsequent degradatio n of I kappaB alpha. On the basis of the data, we suggest that RhoB is a no vel negative regulator of NF-kappaB signaling.