title: Regulation of nuclear proteasome by Rhp6/Ubc2 through ubiquitination and destruction of the sensor and anchor Cut8.
abstract: While proteasome is central to the degradation of cellular ubiquitinated proteins, the control of its nuclear function is barely understood. Here we show that the fission yeast ubiquitin-conjugating Rhp6/Ubc2/Rad6 and ligating enzymes Ubr1 are responsible for nuclear enrichment of proteasome through the function of Cut8, a nuclear envelope protein. Cut8 is an Rhp6 substrate that physically interacts with and tethers proteasome. Nonubiquitinatable K-all-R Cut8 weakly interacts with proteasome and fails to enrich nuclear proteasome. Consistently, the nuclear enrichment of proteasome also fails in rhp6 and ubr1 null mutants. Further, cut8 null and cut8 K-all-R mutants are hypersensitive to DNA damage, probably due to the paucity of nuclear proteasome. Thus, Rhp6 enhances the retention of nuclear proteasome through regulating Cut8. The short-lived nature of Cut8 is crucial for feedback enrichment of the proteasome within the nucleus. This is likely to be a conserved mechanism as we describe a Cut8 homolog in flies.
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Takeda
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yanagida
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D029702:Schizosaccharomyces pombe Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C088892:Cut8 protein, S pombe; D029721:Drosophila Proteins; D029702:Schizosaccharomyces pombe Proteins; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; C063863:rhp6 protein, S pombe; D011494:Protein Kinases; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex