SUMOylation Regulates Polo-like Kinase 1-interacting Checkpoint Helicase (PICH) during Mitosis

Sridharan, Vinidhra; Park, Hyewon; Ryu, Hyunju; Azuma, Yoshiaki

doi:10.1074/jbc.c114.601906

Cited by 23 publications

(36 citation statements)

References 39 publications

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“…Three truncation mutants covering and overlapping the N-and C-terminus portions of PICH were utilized for in vitro pull-down assays using SUMOylated-PARP1 (1-650 a.a.) with XEE expressing the mutants by mRNA addition to the XEE. 10 The C-terminal portion of PICH with amino acids 616-1250 was highly enriched, specifically on SUMOylated-PARP1 (1-650 a.a.) beads (Fig. 1A).…”

Section: Multiple Sim Domains In Pich Mediate Interaction With Sumoylmentioning

confidence: 99%

“…10 To investigate the functional significance of the PICH/SUMO interaction, we utilized human PICH throughout this study and aimed to ascertain potential SIM sequences on PICH. In order to identify the SUMO-interacting regions on PICH, we made PICH truncations.…”

Section: Multiple Sim Domains In Pich Mediate Interaction With Sumoylmentioning

confidence: 99%

“…10 SUMOylation is a posttranslational modification that regulates diverse cellular processes. SUMO modification of a protein can mediate novel protein-protein interaction and alter the protein's localization, activity, and stability.…”

Section: Introductionmentioning

confidence: 99%

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SUMO-interacting motifs (SIMs) in Polo-like kinase 1-interacting checkpoint helicase (PICH) ensure proper chromosome segregation during mitosis

Sridharan

Azuma

2016

Cell Cycle

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Polo-like kinase 1 (Plk1)-interacting checkpoint helicase (PICH) localizes at the centromere and is critical for proper chromosome segregation during mitosis. However, the precise molecular mechanism of PICH's centromeric localization and function at the centromere is not yet fully understood. Recently, using Xenopus egg extract assays, we showed that PICH is a promiscuous SUMO binding protein. To further determine the molecular consequence of PICH/SUMO interaction on PICH function, we identified 3 SUMOinteracting motifs (SIMs) on PICH and generated a SIM-deficient PICH mutant. Using the conditional expression of PICH in cells, we found distinct roles of PICH SIMs during mitosis. Although all SIMs are dispensable for PICH's localization on ultrafine anaphase DNA bridges, only SIM3 (third SIM, close to the Cterminus end of PICH) is critical for its centromeric localization. Intriguingly, the other 2 SIMs function in chromatin bridge prevention. With these results, we propose a novel SUMO-dependent regulation of PICH's function on mitotic centromeres.

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Section: Multiple Sim Domains In Pich Mediate Interaction With Sumoylmentioning

confidence: 99%

Section: Multiple Sim Domains In Pich Mediate Interaction With Sumoylmentioning

confidence: 99%

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SUMO-interacting motifs (SIMs) in Polo-like kinase 1-interacting checkpoint helicase (PICH) ensure proper chromosome segregation during mitosis

Sridharan

Azuma

2016

Cell Cycle

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“…Interestingly, the Polo-like kinase 1-interacting checkpoint helicase (PICH) interacts with SUMOylated TOPO IIα at mitotic chromosomes of Xenopus egg extracts [109]. In addition, PICH also binds to SUMOylated PARP-1 at mitotic chromosomes and SUMOylation of PICH itself inhibits its loading onto DNA.…”

Section: Text Box 1 Sumoylation Regulates Topoisomerase Iiα In Mitosismentioning

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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“…PICH was previously found by the Azuma lab to bind to SUMO-modified PARP1 and TopoIIa 5 . Both PARP1 and TopoIIa localize to centromeres and kinetochores during mitosis and also function in resolving chromatin bridges.…”

mentioning

confidence: 93%