RANGAP1 INDUCED GTPASE ACTIVITY OF NUCLEAR RAS-RELATED RAN

The nuclear Ras-related protein Ran binds guanine nucleotide and is in volved in cell cycle regulation. Models of the signal pathway predict Ran to be active as Ran-GTP at the initiation of S phase upon activati on by the nucleotide exchange factor RCC1 and to be inactivated for th e onset of mitosis by hydrolysis of bound GTP. Here a nuclear homodime ric 65-kDa protein, RanGAP1, is described, which we believe to be the immediate antagonist of RCC1. It was purified from HeLa cell lysates a nd induces GTPase activity of Ran, but not Ras, by more than 3 orders of magnitude. The Ran mutant Q69L, modeled after RasQ61L, which is una ble to hydrolyze bound GTP, is insensitive to RanGAP1.