A SMALL UBIQUITIN-RELATED POLYPEPTIDE INVOLVED IN TARGETING RANGAP1 TO NUCLEAR-PORE COMPLEX PROTEIN RANBP2

We have found that the mammalian Ran GTPase-activating protein RanGAP1 is highly concentrated at the cytoplasmic periphery of the nuclear po re complex (NPC), where it associates with the 358-kDa Ran-GTP-binding protein RanBP2. This interaction requires the ATP-dependent posttrans lational conjugation of RanGAP1 with SUMO-1 (for small ubiquitin-relat ed modifier), a novel protein of 101 amino acids that contains low but significant homology to ubiquitin. SUMO-1 appears to represent the pr ototype for a novel family of ubiquitin-related protein modifiers. Inh ibition of nuclear protein import resulting from antibodies directed a t NPC-associated RanGAP1 cannot be overcome by soluble cytosolic RanGA P1, indicating that GTP hydrolysis by Ran at RanBP2 is required for nu clear protein import.