COACTIVATION OF RANGTPASE AND INHIBITION OF GTP DISSOCIATION BY RAN GTP-BINDING PROTEIN RANBP1

RCC1 (the regulator of chromosome condensation) stimulates guanine nuc leotide dissociation on the Ras-related nuclear protein Ran, Both poly peptides are components of a regulatory pathway that has been implicat ed in regulating DNA replication, onset of and exit from mitosis, mRNA processing and transport, and import of proteins into the nucleus, In a search for further members of the RCC1- Ran signal pathway, we have identified proteins of 23, 45 and 300 kDa which tightly bind to Ran-G TP but not Ran-GDP, The purified soluble 23 kDa Ran binding protein Ra nBP1 does not activate RanGTPase, but increases GTP hydrolysis induced by the RanGTPase-activating protein RanGAP1 by an order of magnitude, In the absence of RanGAP, it strongly inhibits RCC1-induced exchange of Ran-bound GTP. In addition, it forms a stable complex with nucleoti de-free RCC1-Ran, With these properties, it differs markedly from guan ine diphosphate dissociation inhibitors which preferentially prevent t he exchange of protein-bound GDP and in some cases were shown to inhib it GAP-induced GTP hydrolysis, RanBP1 is the first member of a new cla ss of proteins regulating the binding and hydrolysis of GTP by Ras-rel ated proteins.