Zhou, W., Ryan, J. J. & Zhou, H.Global analyses of sumoylated proteins in Saccharomyces cerevisiae. Induction of protein sumoylation by cellular stresses. J. Biol. Chem.279, 32262-32268

Ludwig Institute for Cancer Research, University of California-San Diego, La Jolla, 92093, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 08/2004; 279(31):32262-8. DOI: 10.1074/jbc.M404173200
Source: PubMed


We have undertaken a global analysis of sumoylated proteins in Saccharomyces cerevisiae by tandem mass spectrometry. Exposure of cells to oxidative and ethanol stresses caused large increases in protein sumoylation.
A large number of new sumoylated proteins were identified in untreated, hydrogen peroxide-treated, and ethanol-treated cells.
These proteins are known to be involved in diverse cellular processes, including gene transcription, protein translation,
DNA replication, chromosome segregation, metabolic processes, and stress responses. Additionally, the known enzymes, including
E1, E2, and E3 of the sumoylation cascade were found to be auto-sumoylated. Taken together, these results show that protein
sumoylation is broadly involved in many cellular functions and this mass spectrometry-based proteomic approach is useful in
studying the regulation of protein sumoylation in the cells.

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Available from: Weidong Zhou, May 28, 2015
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    • "Here, the relevant Sumo target still needs to be identified. A good candidate is RNAPII, which was previously shown to be sumoylated, although the exact physiological significance remains unclear (Wohlschlegel et al. 2004; Zhou et al. 2004; Chen et al. 2009). Histones may also be Sumo substrates (Nathan et al. 2006). "
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    ABSTRACT: Transcription factors are abundant Sumo targets, yet the global distribution of Sumo along the chromatin and its physiological relevance in transcription are poorly understood. Using Saccharomyces cerevisiae, we determined the genome-wide localization of Sumo along the chromatin. We discovered that Sumo-enriched genes are almost exclusively involved in translation, such as tRNA genes and ribosomal protein genes (RPGs). Whole-genome expression analysis showed that Sumo positively regulates their transcription. We also discovered that the Sumo consensus motif at RPG promoters is identical to the DNA binding motif of the transcription factor Rap1. We demonstrate that Rap1 is a molecular target of Sumo and that sumoylation of Rap1 is important for cell viability. Furthermore, Rap1 sumoylation promotes recruitment of the basal transcription machinery, and sumoylation of Rap1 cooperates with the target of rapamycin kinase complex 1 (TORC1) pathway to promote RPG transcription. Strikingly, our data reveal that sumoylation of Rap1 functions in a homeostatic feedback loop that sustains RPG transcription during translational stress. Taken together, Sumo regulates the cellular translational capacity by promoting transcription of tRNA genes and RPGs. Published by Cold Spring Harbor Laboratory Press.
    Full-text · Article · Mar 2015 · Genome Research
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    • "Roughly about 500 substrate proteins in budding yeast have been identified as SUMO substrate proteins (Srikumar et al. 2013; Zhou et al. 2004). SUMO is essential for the viability of yeast and regulates diverse biological processes, including DNA repair, transcriptional regulation, protein localization, formation of subnuclear structures, and cell cycle progression (Praefcke et al. 2012; Psakhye and Jentsch 2012; Srikumar et al. 2013; Zhou et al. 2004). In addition, the discovery of SUMO-dependent ubiquitin ligases, such as Slx5-Slx8 and Ris1, has revealed that SUMO enhances protein degradation by binding with ubiquitin (Praefcke et al. 2012; Uzunova et al. 2007). "
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    ABSTRACT: The complex inhibitory effects of inhibitors present in lignocellulose hydrolysate suppress the ethanol fermentation of Saccharomyces cerevisiae. Although the interactive inhibitory effects play important roles in the actual hydrolysate, few studies have investigated glycolaldehyde, the key inhibitor of hot-compressed water-treated lignocellulose hydrolysate. Given this challenge, we investigated the interactive effects of mixed fermentation inhibitors, including glycolaldehyde. First, we confirmed that glycolaldehyde was the most potent inhibitor in the hydrolysate and exerted interactive inhibitory effects in combination with major inhibitors. Next, through genome-wide analysis and megavariate data modeling, we identified SUMOylation as a novel potential mechanism to overcome the combinational inhibitory effects of fermentation inhibitors. Indeed, overall SUMOylation was increased and Pgk1, which produces an ATP molecule in glycolysis by substrate-level phosphorylation, was SUMOylated and degraded in response to glycolaldehyde. Augmenting the SUMO-dependent ubiquitin system in the ADH1-expressing strain significantly shortened the lag phase of growth, released cells from G2/M arrest, and improved energy status and glucose uptake in the inhibitor-containing medium. In summary, our study was the first to establish SUMOylation as a novel platform for regulating the lag phase caused by complex fermentation inhibitors.
    Full-text · Article · Oct 2014 · Applied Microbiology and Biotechnology
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    • "However, the additional observed sumoylation at Lys9 is most likely because of the difference between the assay systems, i.e., in vitro versus in vivo. Consistent with our findings, proteomic analyses have demonstrated SOD1 sumoylation at multiple sites in a yeast system [27], [28]. It should be noted that sumoylated SOD1 was still observed in the lysate of cells transfected with G93R/K9R/K75R-SOD1 triple mutant and SUMO1 (Fig. 1B, lane 4), suggesting the existence of minor sumoylation sites other than Lys9 and Lys75 in human SOD1. "
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    ABSTRACT: Mutations in superoxide dismutase 1 (SOD1) are a major cause of familial amyotrophic lateral sclerosis (ALS), whereby the mutant proteins misfold and aggregate to form intracellular inclusions. We report that both small ubiquitin-like modifier (SUMO) 1 and SUMO2/3 modify ALS-linked SOD1 mutant proteins at lysine 75 in a motoneuronal cell line, the cell type affected in ALS. In these cells, SUMO1 modification occurred on both lysine 75 and lysine 9 of SOD1, and modification of ALS-linked SOD1 mutant proteins by SUMO3, rather than by SUMO1, significantly increased the stability of the proteins and accelerated intracellular aggregate formation. These findings suggest the contribution of sumoylation, particularly by SUMO3, to the protein aggregation process underlying the pathogenesis of ALS.
    Full-text · Article · Jun 2014 · PLoS ONE
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