Comprehensive Identification of SUMO2/3 Targets and Their Dynamics during Mitosis

Schou, Julie; Kelstrup, Christian D.; Hayward, Daniel; Olsen, Jesper V.; Nilsson, Jakob

doi:10.1371/journal.pone.0100692

Cited by 20 publications

(24 citation statements)

References 46 publications

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“…We compared the proteins identified in our study to those of two recent proteomic studies reporting the identification of mitotic SUMO‐2/3 substrates (Fig. A) . In the first study, proteins modified by an exogenously expressed and tagged variant of SUMO‐2 were purified from whole cell lysates prepared from HeLa cells synchronized in mitosis using CDK1 inhibition and release .…”

Section: Resultsmentioning

confidence: 99%

Identification of SUMO-2/3-modified proteins associated with mitotic chromosomes

et al. 2015

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Sumoylation is essential for progression through mitosis, but the specific protein targets and functions remain poorly understood. In this study, we used chromosome spreads to more precisely define the localization of SUMO-2/3 to the inner-centromere and protein scaffold of mitotic chromosomes. We also developed methods to immunopurify proteins modified by endogenous, untagged SUMO-2/3 from mitotic chromosomes. Using these methods we identified 149 chromosome-associated SUMO-2/3 substrates by nLC-ESI-MS/MS. Approximately one-third of the identified proteins have reported functions in mitosis. Consistent with SUMO-2/3 immunolocalization, we identified known centromere and kinetochore associated proteins, as well as chromosome scaffold associated proteins. Notably, >30 proteins involved in chromatin modification or remodeling were identified. Our results provide insights into the roles of sumoylation as a regulator of chromatin structure and other diverse processes in mitosis. Furthermore, our purification and fractionation methodologies represent an important compliment to existing approaches to identify sumoylated proteins using exogenously expressed and tagged SUMOs.

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Section: Resultsmentioning

confidence: 99%

Identification of SUMO-2/3-modified proteins associated with mitotic chromosomes

et al. 2015

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“…For instance, TRIM28, SMC3, SAFB1, and KIF4A were among the validated SUMO substrates . Moreover, Schou et al . investigated global SUMO2/3 modifications in mitosis and upon mitotic exit.…”

Section: Posttranslational Modification Analysis Of Cell Divisionmentioning

confidence: 99%

“…Their analysis revealed that the levels of SUMO2/3 modified proteins such as KLN2 and Repo‐Man increase upon mitotic exit. On the other hand, only a small number of proteins were SUMO2/3 modified in mitosis such as RhoGDIα …”

Section: Posttranslational Modification Analysis Of Cell Divisionmentioning

confidence: 99%

“…For instance, TRIM28, SMC3, SAFB1, and KIF4A were among the validated SUMO substrates. [120] Moreover, Schou et al [121] investigated global SUMO2/3 modifications in mitosis and upon mitotic exit. Mitosis and mitotic exit targets of the SUMO2/3 modification were quantified by SILAC using stably Flag-His tagged SUMO2 expressing cells.…”

Section: Sumoylationmentioning

confidence: 99%

“…On the other hand, only a small number of proteins were SUMO2/3 modified in mitosis such as RhoGDIα. [121] Sumoylation and phosphorylation crosstalk may be one of the mechanisms regulating the cell cycle progression. Yao et al [122] analyzed the effect of sumoylation changes on the global phosphoproteome.…”

Section: Sumoylationmentioning

confidence: 99%

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Proteomics in Cell Division

et al. 2017

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Cell division requires a coordinated action of the cell cycle machinery, cytoskeletal elements, chromosomes, and membranes. Cell division studies have greatly benefitted from the mass spectrometry (MS)-based proteomic approaches for probing the biochemistry of highly dynamic complexes and their coordination with each other as a cell progresses into division. In this review, the authors first summarize a wide-range of proteomic studies that focus on the identification of sub-cellular components/protein complexes of the cell division machinery including kinetochores, mitotic spindle, midzone, and centrosomes. The authors also highlight MS-based large-scale analyses of the cellular components that are largely understudied during cell division such as the cell surface and lipids. Then, the authors focus on posttranslational modification analyses, especially phosphorylation and the resulting crosstalk with other modifications as a cell undergoes cell division. Combining proteomic approaches that probe the biochemistry of cell division components with functional genomic assays will lead to breakthroughs toward a systems-level understanding of cell division.

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2‐O‐Octadecylascorbic acid represses RhoGDIβ expression and ameliorates DNA damage‐induced abnormal spindle orientations

Doi

Togari

Minagi

et al. 2021

J of Cellular Biochemistry

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The appropriate regulation of spindle orientation maintains proper tissue homeostasis and avoids aberrant tissue repair or regeneration. Spindle misorientation due to imbalance or improper functioning leads to a loss of tissue integrity and aberrant growth, such as tissue loss or overgrowth. Pharmacological manipulation to prevent spindle misorientation will enable a better understanding of how spindle orientation is involved in physiological and pathological conditions and will provide therapeutic possibilities to treat patients associated with abnormal tissue function caused by spindle misorientation. N‐terminal‐deleted Rho guanine nucleotide dissociation inhibitor β (RhoGDIβ/RhoGDI2/LyGDI) produced by caspase‐3 activation perturbs spindle orientation in surviving cells following exposure to either ionizing radiation or UVC. Thus, presumably, RhoGDIβ cleaved by caspase‐3 activation acts as a determinant of radiation‐induced spindle misorientation that promote aberrant tissue repair due to deregulation of directional organization of cell population and therefore becomes a potential target of drugs to prevent such response. The objective of this study was to screen and identify chemicals that suppress RhoGDIβ expression. We focused our attention on ascorbic acid (AA) derivatives because of their impact on the maintenance of skin tissue homeostasis. Here, we screened for AA derivatives that suppress RhoGDIβ expression in HeLa cells and identified a lipophilic derivative, 2‐O‐octadecylascorbic acid (2‐OctadecylAA), as a novel RhoGDIβ inhibitor that ameliorated ionizing radiation‐induced abnormal spindle orientations. Among all examined AA derivatives, which were also antioxidative, the inhibition activity was specific to 2‐OctadecylAA. Therefore, this activity was not due to simple antioxidant properties. 2‐OctadecylAA was previously shown to prevent hepatocellular carcinoma development. Our findings suggest that the anticarcinogenic effects of 2‐OctadecylAA are partly due to RhoGDIβ inhibition mechanisms by which spindle orientation perturbations are attenuated. Thus, the molecular targeting features of RhoGDIβ warrant its further development for the treatment or control of spindle orientation abnormalities that affect epithelial homeostasis.

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Comprehensive Identification of SUMO2/3 Targets and Their Dynamics during Mitosis

Cited by 20 publications

References 46 publications

Identification of SUMO-2/3-modified proteins associated with mitotic chromosomes

Identification of SUMO-2/3-modified proteins associated with mitotic chromosomes

Proteomics in Cell Division

2‐O‐Octadecylascorbic acid represses RhoGDIβ expression and ameliorates DNA damage‐induced abnormal spindle orientations

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