title: Unconventional tethering of Ulp1 to the transport channel of the nuclear pore complex by karyopherins.
abstract: The ubiquitin-like protein SUMO-1 (small ubiquitin-related modifier 1) is covalently attached to substrate proteins by ligases and cleaved by isopeptidases. Yeast has two SUMO-1-deconjugating enzymes, Ulp1 and Ulp2, which are located at nuclear pores and in the nucleoplasm, respectively. Here we show that the catalytic C-domain of Ulp1 must be excluded from the nucleoplasm for cell viability. This is achieved by the noncatalytic N-domain, which tethers Ulp1 to the nuclear pores. The bulk of cellular Ulp1 is not associated with nucleoporins but instead associates with three karyopherins (Pse1, Kap95 and Kap60), in a complex that is not dissociated by RanGTP in vitro. The Ulp1 N-domain has two distinct binding sites for Pse1 and Kap95/Kap60, both of which are required for anchoring to the nuclear pore complex. We propose that Ulp1 is tethered to the nuclear pores by a Ran-insensitive interaction with karyopherins associated with nucleoporins. This location could allow Ulp1 to remove SUMO-1 from sumoylated cargo proteins during their passage through the nuclear pore channel.
authors.affiliation: BZH, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany.
authors.forename: Vikram Govind
authors.initials: VG
authors.lastname: Panse
authors.forename: Bernhard
authors.initials: B
authors.lastname: Küster
authors.forename: Thomas
authors.initials: T
authors.lastname: Gerstberger
authors.forename: Ed
authors.initials: E
authors.lastname: Hurt
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D001692:Biological Transport; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005799:Genes, Dominant; D005804:Genes, Lethal; D028884:Karyopherins / Q000378:metabolism*; D022022:Nuclear Pore / Q000502:physiology*; D025842:SUMO-1 Protein / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D028884:Karyopherins; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D003546:Cysteine Endopeptidases; C118083:Ulp1 protease