title: Targeting of SUMO substrates to a Cdc48-Ufd1-Npl4 segregase and STUbL pathway in fission yeast.
abstract: In eukaryotes, the conjugation of proteins to the small ubiquitin-like modifier (SUMO) regulates numerous cellular functions. A proportion of SUMO conjugates are targeted for degradation by SUMO-targeted ubiquitin ligases (STUbLs) and it has been proposed that the ubiquitin-selective chaperone Cdc48/p97-Ufd1-Npl4 facilitates this process. However, the extent to which the two pathways overlap, and how substrates are selected, remains unknown. Here we address these questions in fission yeast through proteome-wide analyses of SUMO modification sites. We identify over a thousand sumoylated lysines in a total of 468 proteins and quantify changes occurring in the SUMO modification status when the STUbL or Ufd1 pathways are compromised by mutations. The data suggest the coordinated processing of several classes of SUMO conjugates, many dynamically associated with centromeres or telomeres. They provide new insights into subnuclear organization and chromosome biology, and, altogether, constitute an extensive resource for the molecular characterization of SUMO function and dynamics.
authors.affiliation: Department of Biology, University of Copenhagen, Ole MaalÃ¸es vej 5, Copenhagen DK-2200, Denmark.
authors.forename: Julie Bonne
authors.initials: JB
authors.lastname: Køhler
authors.affiliation: Centre for Gene Regulation and Expression, Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Triin
authors.initials: T
authors.lastname: Tammsalu
authors.affiliation: Department of Biology, University of Copenhagen, Ole MaalÃ¸es vej 5, Copenhagen DK-2200, Denmark.
authors.forename: Maria Mønster
authors.initials: MM
authors.lastname: Jørgensen
authors.affiliation: Department of Biology, University of Copenhagen, Ole MaalÃ¸es vej 5, Copenhagen DK-2200, Denmark.
authors.forename: Nana
authors.initials: N
authors.lastname: Steen
authors.affiliation: Centre for Gene Regulation and Expression, Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Ronald Thomas
authors.identifier: http://orcid.org/0000-0001-7113-9024
authors.initials: RT
authors.lastname: Hay
authors.affiliation: Department of Biology, University of Copenhagen, Ole MaalÃ¸es vej 5, Copenhagen DK-2200, Denmark.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Thon
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002503:Centromere / Q000378:metabolism; D008364:Mannosyltransferases / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D058207:Sumoylation; D016615:Telomere / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D000074405:Valosin Containing Protein; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C104361:NPL4 protein, S cerevisiae; C576270:Npl4 protein, S pombe; D029543:Nucleocytoplasmic Transport Proteins; C402486:Pmt3 protein, S pombe; D012097:Repressor Proteins; C522602:Rfp1 protein, S pombe; C522603:Rfp2 protein, S pombe; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C444652:UFD1 protein, S cerevisiae; C576269:Ufd1 protein, S pombe; D033921:Vesicular Transport Proteins; D043743:Ubiquitin-Protein Ligase Complexes; C515574:Slx8 protein, S cerevisiae; C587431:Slx8 protein, S pombe; D044767:Ubiquitin-Protein Ligases; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein; C515573:Slx5 protein, S cerevisiae