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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Cycle Proteins / biosynthesis
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Nucleus / metabolism*
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Drosophila
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Drosophila Proteins / genetics
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Molecular Sequence Data
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Mutation
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Proteasome Endopeptidase Complex / metabolism*
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Protein Kinases / genetics
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases
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Schizosaccharomyces pombe Proteins / biosynthesis
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Schizosaccharomyces pombe Proteins / genetics
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Schizosaccharomyces pombe Proteins / metabolism*
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Sequence Alignment
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Sequence Homology, Amino Acid
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Ubiquitin / metabolism*
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Ubiquitin-Conjugating Enzymes / genetics
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Ubiquitin-Conjugating Enzymes / metabolism*
Substances
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Cell Cycle Proteins
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Cut8 protein, S pombe
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Drosophila Proteins
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Schizosaccharomyces pombe Proteins
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Ubiquitin
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Ubiquitin-Conjugating Enzymes
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rhp6 protein, S pombe
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Protein Kinases
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Bub1 spindle checkpoint protein
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Protein Serine-Threonine Kinases
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Proteasome Endopeptidase Complex