SUMO-1 Modification and Its Role in Targeting the Ran GTPase-activating Protein, RanGAP1, to the Nuclear Pore Complex
Open Access
- 9 February 1998
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 140 (3) , 499-509
- https://doi.org/10.1083/jcb.140.3.499
Abstract
RanGAP1 is the GTPase-activating protein for Ran, a small ras-like GTPase involved in regulating nucleocytoplasmic transport. In vertebrates, RanGAP1 is present in two forms: one that is cytoplasmic, and another that is concentrated at the cytoplasmic fibers of nuclear pore complexes (NPCs). The NPC-associated form of RanGAP1 is covalently modified by the small ubiquitin-like protein, SUMO-1, and we have recently proposed that SUMO-1 modification functions to target RanGAP1 to the NPC. Here, we identify the domain of RanGAP1 that specifies SUMO-1 modification and demonstrate that mutations in this domain that inhibit modification also inhibit targeting to the NPC. Targeting of a heterologous protein to the NPC depended on determinants specifying SUMO-1 modification and also on additional determinants in the COOH-terminal domain of RanGAP1. SUMO-1 modification and these additional determinants were found to specify interaction between the COOH-terminal domain of RanGAP1 and a region of the nucleoporin, Nup358, between Ran-binding domains three and four. Together, these findings indicate that SUMO-1 modification targets RanGAP1 to the NPC by exposing, or creating, a Nup358 binding site in the COOH-terminal domain of RanGAP1. Surprisingly, the COOH-terminal domain of RanGAP1 was also found to harbor a nuclear localization signal. This nuclear localization signal, and the presence of nine leucine-rich nuclear export signal motifs, suggests that RanGAP1 may shuttle between the nucleus and the cytoplasm.Keywords
This publication has 69 references indexed in Scilit:
- Disassembly of RanGTP-Karyopherin β Complex, an Intermediate in Nuclear Protein ImportPublished by Elsevier ,1997
- A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex.The Journal of cell biology, 1996
- Associations of UBE2I with RAD52, UBL1, p53, and RAD51 Proteins in a Yeast Two-Hybrid SystemGenomics, 1996
- HIV Rev uses a conserved cellular protein export pathway for the nucleocytoplasmic transport of viral RNAsCurrent Biology, 1996
- Cloning and Expression of Human Homolog HSMT3 to Yeast SMT3 Suppressor of MIF2 Mutations in a Centromere Protein GeneBiochemical and Biophysical Research Communications, 1996
- Role of the Nuclear Transport Factor p10 in Nuclear ImportScience, 1996
- The small nuclear GTPase Ran: How much does it run?BioEssays, 1996
- Conjugation of the 15-kDa Interferon-induced Ubiquitin Homolog Is Distinct from That of UbiquitinJournal of Biological Chemistry, 1996
- Roles of Ubiquitinylation in Proteolysis and Cellular RegulationAnnual Review of Nutrition, 1995
- Identification of cytosolic factors required for nuclear location sequence-mediated binding to the nuclear envelope.The Journal of cell biology, 1994