RanGAP1 induces GTPase activity of nuclear Ras-related Ran.
The nuclear Ras-related protein Ran binds guanine nucleotide and is involved in cell cycle regulation. Models of the signal pathway predict Ran to be active as Ran.GTP at the initiation of S phase upon activation by the nucleotide exchange factor RCC1 and to be inactivated for the onset of mitosis by hydrolysis of bound GTP. Here a nuclear homodimeric 65-kDa protein, RanGAP1, is described, which we believe to be the immediate antagonist of RCC1. It was purified from HeLa cell lysates and induces GTPase activity of Ran, but not Ras, by more than 3 orders of magnitude. The Ran mutant Q69L, modeled after RasQ61L, which is unable to hydrolyze bound GTP, is insensitive to RanGAP1.
Bischoff
F R
FR
Division for Molecular Biology of Mitosis, German Cancer Research Center, Heidelberg, Federal Republic of Germany.
Klebe
C
C
Kretschmer
J
J
Wittinghofer
A
A
Ponstingl
H
H
D002451:Cell Compartmentation; D004790:Enzyme Induction / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D020690:GTPase-Activating Proteins; D006367:HeLa Cells; D006801:Humans; D008970:Molecular Weight; D009154:Mutation; D009687:Nuclear Proteins / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction; D013379:Substrate Specificity; D020931:ran GTP-Binding Protein; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020931:ran GTP-Binding Protein