Køhler Julie Bonne, Tammsalu Triin, Jørgensen Maria Mønster, Steen Nana, Hay Ronald Thomas, Thon Geneviève
Department of Biology, University of Copenhagen, Ole Maaløes vej 5, Copenhagen DK-2200, Denmark.
Centre for Gene Regulation and Expression, Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Nat Commun. 2015 Nov 5;6:8827. doi: 10.1038/ncomms9827.
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.
在真核生物中，蛋白质与小泛素样修饰物（SUMO）的缀合调节着众多细胞功能。一部分SUMO缀合物会被SUMO靶向泛素连接酶（STUbL）靶向降解，有人提出泛素选择性伴侣蛋白Cdc48/p97-Ufd1-Npl4促进了这一过程。然而，这两条途径的重叠程度以及底物的选择方式仍不清楚。在这里，我们通过对SUMO修饰位点进行全蛋白质组分析，在裂殖酵母中解决了这些问题。我们在总共468种蛋白质中鉴定出一千多个SUMO化赖氨酸，并量化了STUbL或Ufd1途径因突变而受损时SUMO修饰状态发生的变化。数据表明几类SUMO缀合物是协同加工的，其中许多与着丝粒或端粒动态相关。它们为核内亚结构组织和染色体生物学提供了新的见解，总体而言，构成了一个用于SUMO功能和动态分子表征的广泛资源。
