Increased p21ras-specific Guanine-nucleotide exchange causes tumor-formation in nude-mice

RAS activation state is set by GTPase Activating Proteins (GAP) and Guanine Nucleotide Releasing Proteins (GNRP). The latter were discovered in yeast as the products of the CDC25 and SDC25 genes; two protein families with homologous catalytic domains but different structural organization exist also in mammals. We show that the C-terminal, catalytic domain of a mouse homologue of CDC25 transactivates the ras-responsive fos promoter in vivo. The increased p21ras-specific guanine nucleotide releasing activity of fibroblasts expressing CDC25Mm catalytic domain correlates with tumor induction in nude mice, suggesting that deregulation of these proteins may be important in tumor development.