The ubiquitin-proteasome system is a key component of the SUMO-2/3 cycle

Joost Schimmel, Katja M. Larsen, Ivan Matic, Martijn van Hagen, Jürgen Cox, Matthias Mann, Jens S. Andersen, Alfred C. O. Vertegaal

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    118 Citations (Scopus)

    Abstract

    Many proteins are regulated by a variety of post-translational modifications, and orchestration of these modifications is frequently required for full control of activity. Currently little is known about the combinatorial activity of different post-translational modifications. Here we show that extensive cross-talk exists between sumoylation and ubiquitination. We found that a subset of SUMO-2-conjugated proteins is subsequently ubiquitinated and degraded by the proteasome. In a screen for preferential SUMO-1 or SUMO-2 target proteins, we found that ubiquitin accumulated in purified SUMO-2 conjugates but not in SUMO-1 conjugates. Upon inhibition of the proteasome, the amount of ubiquitin in purified SUMO-2 conjugates increased. In addition, we found that endogenous SUMO-2/3 conjugates, but not endogenous SUMO-1 conjugates, accumulated in response to proteasome inhibitors. Quantitative proteomics experiments enabled the identification of 73 SUMO-2-conjugated proteins that accumulated in cells treated with proteasome inhibitors. Cross-talk between SUMO-2/3 and the ubiquitin-proteasome system controls many target proteins that regulate all aspects of nucleic acid metabolism. Surprisingly the relative abundance of 40 SUMO-2-conjugated proteins was reduced by proteasome inhibitors possibly because of a lack of recycled SUMO-2. We conclude that SUMO-2/3 conjugation and the ubiquitin-proteasome system are tightly integrated and act in a cooperative manner. Molecular & Cellular Proteomics 7: 2107-2122, 2008.

    Original languageEnglish
    Pages (from-to)2107-2122
    Number of pages16
    JournalMolecular & Cellular Proteomics
    Volume7
    Issue number11
    DOIs
    Publication statusPublished - 1 Nov 2008

    Keywords

    • TARGET PROTEINS
    • KAPPA-B ACTIVATION
    • NUCLEAR-PORE COMPLEX
    • DNA-REPAIR
    • RNF4
    • GENOME STABILITY
    • DEGRADATION
    • QUANTITATIVE PROTEOMICS
    • PML
    • SACCHAROMYCES-CEREVISIAE

    Cite this

    Schimmel, J., Larsen, K. M., Matic, I., van Hagen, M., Cox, J., Mann, M., Andersen, J. S., & Vertegaal, A. C. O. (2008). The ubiquitin-proteasome system is a key component of the SUMO-2/3 cycle. Molecular & Cellular Proteomics, 7(11), 2107-2122. https://doi.org/10.1074/mcp.M800025-MCP200