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Site-specific characterization of endogenous SUMOylation across species and organs.

Nature communications | 2018

Small ubiquitin-like modifiers (SUMOs) are post-translational modifications that play crucial roles in most cellular processes. While methods exist to study exogenous SUMOylation, large-scale characterization of endogenous SUMO2/3 has remained technically daunting. Here, we describe a proteomics approach facilitating system-wide and in vivo identification of lysines modified by endogenous and native SUMO2. Using a peptide-level immunoprecipitation enrichment strategy, we identify 14,869 endogenous SUMO2/3 sites in human cells during heat stress and proteasomal inhibition, and quantitatively map 1963 SUMO sites across eight mouse tissues. Characterization of the SUMO equilibrium highlights striking differences in SUMO metabolism between cultured cancer cells and normal tissues. Targeting preferences of SUMO2/3 vary across different organ types, coinciding with markedly differential SUMOylation states of all enzymes involved in the SUMO conjugation cascade. Collectively, our systemic investigation details the SUMOylation architecture across species and organs and provides a resource of endogenous SUMOylation sites on factors important in organ-specific functions.

Pubmed ID: 29942033 RIS Download

Associated grants

  • Agency: Natur og Univers, Det Frie Forskningsråd (Natural Sciences, Danish Council for Independent Research), International
    Id: DFF 4002-00051
  • Agency: Sundhed og Sygdom, Det Frie Forskningsråd (Medical Sciences, Danish Council for Independent Research), International
    Id: DFF 4183-00322A

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ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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RRID:SCR_008628

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RRID:SCR_001572

Service that searches carbohydrate structures for motifs commonly used for carbohydrate classification, like N- and O-glycan cores, Lewis antigens, etc. Note: Sumo is currently under construction. Motif searches are a frequently used tool in proteomics. For carbohydrate structures, there are also many motifs classified in the literature, e.g. the Lewis antigens or the diverse O-glycan core structures. Sumo is a tool to locate such motifs in a carbohydrate structure given in LINUCS or in IUPAC nomenclature.

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RRID:SCR_002380

Collection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.

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RRID:SCR_002456

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RRID:SCR_004055

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RRID:SCR_011819

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RRID:SCR_012137

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RRID:SCR_013651

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RRID:SCR_014485

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RRID:SCR_015753

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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