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

Cubeñas-Potts, Caelin; Srikumar, Tharan; Lee, Christine; Osula, Omoruyi; Subramonian, Divya; Zhang, Xiang Dong; Cotter, Robert J.; Raught, Brian; Matunis, Michael J.

doi:10.1002/pmic.201400400

Cited by 36 publications

(37 citation statements)

References 48 publications

(73 reference statements)

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“…This localization pattern is reminiscent of that of SUMO-1 and SUMO-2/3 during mitosis (Zhang et al., 2008), and the only SUMO isoform in nematodes displays a combination of these localization patterns during the first embryonic mitotic division (Pelisch et al., 2014). Many SUMO substrates are involved in chromatin structure and function (Cubeñas-Potts and Matunis, 2013), and KIF4A, the human ortholog of KLP-19, has been identified as a SUMO substrate in mitotic chromatin (Cubeñas-Potts et al., 2015). These observations support the notion that while precise mechanisms that guarantee proper chromosome orientation, congression, and segregation might differ between meiosis and mitosis and also among species, SUMO is likely a key contributor to a timely and accurate regulation of protein interactions within narrow spatial and temporal windows.…”

Section: Discussionmentioning

confidence: 99%

A SUMO-Dependent Protein Network Regulates Chromosome Congression during Oocyte Meiosis

et al. 2017

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SummaryDuring Caenorhabditis elegans oocyte meiosis, a multi-protein ring complex (RC) localized between homologous chromosomes, promotes chromosome congression through the action of the chromokinesin KLP-19. While some RC components are known, the mechanism of RC assembly has remained obscure. We show that SUMO E3 ligase GEI-17/PIAS is required for KLP-19 recruitment to the RC, and proteomic analysis identified KLP-19 as a SUMO substrate in vivo. In vitro analysis revealed that KLP-19 is efficiently sumoylated in a GEI-17-dependent manner, while GEI-17 undergoes extensive auto-sumoylation. GEI-17 and another RC component, the kinase BUB-1, contain functional SUMO interaction motifs (SIMs), allowing them to recruit SUMO modified proteins, including KLP-19, into the RC. Thus, dynamic SUMO modification and the presence of SIMs in RC components generate a SUMO-SIM network that facilitates assembly of the RC. Our results highlight the importance of SUMO-SIM networks in regulating the assembly of dynamic protein complexes.

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Section: Discussionmentioning

confidence: 99%

A SUMO-Dependent Protein Network Regulates Chromosome Congression during Oocyte Meiosis

et al. 2017

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“…In recent years, several efforts have been made to study sumoylation on a global and site-specific manner by high resolution mass spectrometry (14,15,(51)(52)(53)(54). Reanalyzing all these available data sets (13) revealed that at physiological conditions, at least half of the SUMO substrates are modified at the minimal KxE motif, although upon stress, more lysines at non-SCM sites are modified.…”

Section: The Sumo Consensus Motifmentioning

confidence: 99%

“…Indeed, more than 1000 sumoylated proteins have been identified, with the numbers continuously increasing (13). Sumoylation is highly dynamic and the global SUMO proteome is constantly changing, for example, during cell cycle progression and cell differentiation, and it is drastically induced upon stress (14)(15)(16)(17). Such stress stimuli include DNA damage, heat shock, proteasomal inhibition, viral infection or ischemic challenge.…”

Section: Introductionmentioning

confidence: 99%

SUMO conjugation – a mechanistic view

Pichler

Fatouros

Lee

et al. 2017

Biomolecular Concepts

218

223

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Abstract:The regulation of protein fate by modification with the small ubiquitin-related modifier (SUMO) plays an essential and crucial role in most cellular pathways. Sumoylation is highly dynamic due to the opposing activities of SUMO conjugation and SUMO deconjugation. SUMO conjugation is performed by the hierarchical action of E1, E2 and E3 enzymes, while its deconjugation involves SUMO-specific proteases. In this review, we summarize and compare the mechanistic principles of how SUMO gets conjugated to its substrate. We focus on the interplay of the E1, E2 and E3 enzymes and discuss how specificity could be achieved given the limited number of conjugating enzymes and the thousands of substrates.

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“…These proteomic approaches have also greatly helped in identifying other SUMO target proteins essential for cell cycle progression and have uncovered global SUMO dynamics throughout the cell cycle [23,55]. It would be interesting to identify groups of specific substrates regulated by the different dynamic SUMO machinery components.…”

Section: Sumoylation and Cyclin-dependent Kinases In Concertmentioning

confidence: 99%

“…Additional CDKs and cyclins have been identified as SUMO targets in recent proteomic screens and targeted approaches, including CDK1, CDK9, CDK11 and Cyclin-E, further highlighting crosstalk between SUMOylation and phosphorylation during cell cycle regulation [23,48,54] (Figure 2). These proteomic approaches have also greatly helped in identifying other SUMO target proteins essential for cell cycle progression and have uncovered global SUMO dynamics throughout the cell cycle [23,55]. It would be interesting to identify groups of specific substrates regulated by the different dynamic SUMO machinery components.…”

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confidence: 99%

SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer

Eifler

Vertegaal

2015

Trends in Biochemical Sciences

243

211

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SUMOylation plays critical roles during cell cycle progression. Many important cell cycle regulators, including many oncogenes and tumor suppressors, are functionally regulated via SUMOylation. The dynamic SUMOylation pattern observed throughout the cell cycle is ensured via distinct spatial and temporal regulation of the SUMO machinery. Additionally, SUMOylation cooperates with other post-translational modifications to mediate cell cycle progression. Deregulation of these SUMOylation and deSUMOylation enzymes causes severe defects in cell proliferation and genome stability. Different types of cancers were recently shown to be dependent on a functioning SUMOylation system, a finding that could potentially be exploited in anti-cancer therapies. KeywordsSUMO; mitosis; SUMOylation; cancer; cell cycle SUMO: a ubiquitin-like modifier that regulates nuclear processesThe complexity of eukaryotic proteomes is widely expanded by protein processing and a vast array of posttranslational modifications. The quick and reversible attachment of small modifiers is essential for all cellular processes and ensures dynamic and rapid responses to extracellular and intracellular stimuli. Apart from chemical modifications such as phosphorylation [1], glycosylation [2] and acetylation [3], small polypeptides can be attached to proteins, resulting in a change in the activity, localization, half-life or interactome of the target protein. Since the initial discovery of ubiquitin, the founding member of these small protein posttranslational modifications in 1975 [4], a large family of structurally related ubiquitin-like modifiers has been uncovered including SUMO, Nedd8, ISG15, FAT10, FUB1, UFM1, URM1, Atg12 and Atg8 [5][6][7][8]. The attachment of these small ubiquitin-like modifiers is catalysed by an enzymatic cascade consisting of an activating enzyme (E1), a conjugating enzyme (E2) and a ligase (E3), and can be reversed by specific and cell cycle control. It is therefore not surprising that SUMO signal transduction has been implicated in the development of several different cancer types, which could potentially be exploited in anti-cancer therapies. In this review we will focus on the role of SUMO in cell cycle regulation, specifically highlighting its physiological relevance and its deregulation in cancer. Recent progress includes the identification of many novel SUMO substrates with important roles in cell cycle progression using proteomic approaches, and the demonstration that different mouse cancer models are dependent on a functioning SUMOylation system. Switching of SUMOylation in these cancer models caused a proliferation block of the cancer cells, showing that SUMO conjugating enzymes are potential drug targets. Europe PMC Funders Group Twenty years of SUMO research in cell cycle controlSUMO was linked to cell cycle progression even before the identification of the small protein modifier itself. Twenty years ago, the yeast SUMO conjugating enzyme Ubc9 was first proposed to be a ubiquitin conjugating enzyme. Ubc9 was s...

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

Cited by 36 publications

References 48 publications

A SUMO-Dependent Protein Network Regulates Chromosome Congression during Oocyte Meiosis

A SUMO-Dependent Protein Network Regulates Chromosome Congression during Oocyte Meiosis

SUMO conjugation – a mechanistic view

SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer

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