Comparative proteomic analysis identifies a role for SUMO in protein quality control

Michael H. Tatham, Ivan Matic, Matthias Mann, Ronald T. Hay

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    127 Citations (Scopus)

    Abstract

    The small ubiquitin-like modifiers (SUMOs) alter the functions of diverse cellular proteins by covalent posttranslational modification and thus influence many cellular functions, including gene transcription, cell cycle, and DNA repair. Although conjugation by ubiquitin and SUMO-2/3 are largely functionally and mechanistically independent from one another, both appear to increase under conditions of proteasome inhibition. To better understand the relationship between SUMO and protein degradation by the proteasome, we performed a quantitative proteomic analysis of SUMO-2 substrates after short-and long-term inhibition of the proteasome with MG132. Comparisons with changes to the SUMO-2 conjugate subproteome in response to heat stress revealed qualitative and quantitative parallels between both conditions; however, in contrast to heat stress, the MG132-triggered increase in SUMO-2 conjugation depended strictly on protein synthesis, implying that the accumulation of newly synthesized, misfolded proteins destined for degradation by the proteasome triggered the SUMO conjugation response. Furthermore, proteasomal inhibition resulted in the accumulation of conjugated forms of all SUMO paralogs in insoluble protein inclusions and in the accumulation on SUMO-2 substrates of lysine-63-linked polyubiquitin chains, which are not thought to serve as signals for proteasome-mediated degradation. Together, these findings suggest multiple, proteasome-independent roles for SUMOs in the cellular response to the accumulation of misfolded proteins.

    Original languageEnglish
    Article numberrs4
    Pages (from-to)-
    Number of pages12
    JournalScience Signaling
    Volume4
    Issue number178
    DOIs
    Publication statusPublished - 21 Jun 2011

    Keywords

    • KAPPA-B ACTIVATION
    • QUANTITATIVE PROTEOMICS
    • CHROMOSOME SEGREGATION
    • MASS-SPECTROMETRY
    • TARGET PROTEINS
    • IN-VITRO
    • UBIQUITIN
    • DEGRADATION
    • CHAINS
    • DISEASE

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