The condensin component NCAPG2 regulates microtubule–kinetochore attachment through recruitment of Polo-like kinase 1 to kinetochores

Kim, Jae Hyeong; Shim, Ju Hyun; Ji, Min-Ju; Jung, Youngsoo; Bong, Seoung Min; Jang, Young-Joo; Yoon, Eun-Kyung; Lee, Sang-Jin; Kim, Kwang Gi; Kim, Yon Hui; Lee, Chang-Woo; Lee, Byung Il; Kim, Kyung‐Tae

doi:10.1038/ncomms5588

Cited by 47 publications

(39 citation statements)

References 57 publications

(103 reference statements)

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“…Mouse ESCs were karyotyped as described . Briefly, cells were harvested after 6 hours of colcemid (100 ng/ml) treatment and incubated sequentially in a hypertonic solution (0.075 M KCl) and a fixing solution (methanol/acetic acid, 3:1).…”

Section: Methodsmentioning

confidence: 99%

Core Pluripotency Factors Directly Regulate Metabolism in Embryonic Stem Cell to Maintain Pluripotency

Kim¹,

Jang

Kim³

et al. 2015

Stem Cells

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Pluripotent stem cells (PSCs) have distinct metabolic properties that support their metabolic and energetic needs and affect their stemness. In particular, high glycolysis is critical for the generation and maintenance of PSCs. However, it is unknown how PSCs maintain and acquire this metabolic signature. In this study, we found that core pluripotency factors regulate glycolysis directly by controlling the expression of glycolytic enzymes. Specifically, Oct4 directly governs Hk2 and Pkm2, which are important glycolytic enzymes that determine the rate of glycolytic flux. The overexpression of Hk2 and Pkm2 sustains high levels of glycolysis during embryonic stem cell (ESC) differentiation. Moreover, the maintenance of high glycolysis levels by Hk2 and Pkm2 overexpression hampers differentiation and preserves the pluripotency of ESCs in the absence of leukemia inhibitory factor. Overall, our study identifies a direct molecular connection between core pluripotency factors and ESC metabolic signatures and demonstrates the significance of metabolism in cell fate determination. STEM CELLS 2015;33:2699-2711 SIGNIFICANCE STATEMENTAlthough distinct metabolic properties are critical for the generation and maintenance of Pluripotent stem cells (PSCs), it is unknown how PSCs maintain and acquire this metabolic signature. In this study, we found that core pluripotency factors regulated glycolysis directly by targeting key glycolytic enzymes in embryonic stem cells (ESCs). Furthermore, we found that sustainment of high glycolytic flux delays ESC differentiation and enables certain populations of ESCs to retain the capacity for self-renewal and differentiation potential in the absence of LIF, demonstrating the significance of metabolism in stemness regulation and cell fate determination.

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Section: Methodsmentioning

confidence: 99%

Core Pluripotency Factors Directly Regulate Metabolism in Embryonic Stem Cell to Maintain Pluripotency

Kim¹,

Jang

Kim³

et al. 2015

Stem Cells

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“…Abnormal condensin distribution on mitotic chromosomes correlated with diminished Plk1 enrichment at pericentromeric regions. A previous study on human cells showed that stable localization of Plk1 to the kinetochores requires an interaction with the condensin II subunit Ncapg2 (Kim et al, 2014). Plk1 is required for stabilizing kinetochore-microtubule attachments by counteracting the spindle assembly checkpoint function of Aurora B (Suijkerbuijk et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Condensins are phosphorylated by Cdk1, Plk1 and Aurora B kinases to ensure proficient chromosome condensation (Abe et al, 2011;Lipp et al, 2007;Tada et al, 2011). In addition, condensins are required for appropriate localization of Aurora B and Plk1 kinases during the prophase-to-metaphase transition and ensure accurate chromosome segregation (Abe et al, 2011;Kim et al, 2014;Green et al, 2012;Kitagawa and Lee, 2015). Components of the Smc5/6 complex have been reported to be phosphorylated by Plk1 and Aurora B kinases during mitosis (Hegemann et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Conditional mutation of Smc5 in mouse embryonic stem cells perturbs condensin localization and mitotic progression

Pryzhkova¹,

Jordan²

2016

Development

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Correct duplication of stem cell genetic material and its appropriate segregation into daughter cells are requisites for tissue, organ and organism homeostasis. Disruption of stem cell genomic integrity can lead to developmental abnormalities and cancer. Roles of the Smc5/6 structural maintenance of chromosomes complex in pluripotent stem cell genome maintenance have not been investigated, despite its important roles in DNA synthesis, DNA repair and chromosome segregation as evaluated in other model systems. Using mouse embryonic stem cells (mESCs) with a conditional knockout allele of Smc5, we showed that Smc5 protein depletion resulted in destabilization of the Smc5/6 complex, accumulation of cells in G2 phase of the cell cycle and apoptosis. Detailed assessment of mitotic mESCs revealed abnormal condensin distribution and perturbed chromosome segregation, accompanied by irregular spindle morphology, lagging chromosomes and DNA bridges. Mutation of Smc5 resulted in retention of Aurora B kinase and enrichment of condensin on chromosome arms. Furthermore, we observed reduced levels of Polo-like kinase 1 at kinetochores during mitosis. Our study reveals crucial requirements of the Smc5/6 complex during cell cycle progression and for stem cell genome maintenance.

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“…In 2014, Kim et al . found that NCAPG2 interacts with Polo‐like kinase 1 (PLK1) during the prometaphase–metaphase transition during mitosis and was a new critical player in PLK1 kinetochore localization. NCAPG2 localization and PLK1 recruitment to the kinetochores of misaligned chromosomes are critical for the completion of proper chromosome alignment.…”

Section: Introductionmentioning

confidence: 99%

NCAPG2 promotes tumour proliferation by regulating G2/M phase and associates with poor prognosis in lung adenocarcinoma

Zhan

Zhang

et al. 2016

J Cellular Molecular Medi

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NCAPG2 is a component of the condensin II complex and contributes to chromosome segregation via microtubule–kinetochore attachment during mitosis. It is well known that NCAPG2 plays a critical role in cell mitosis; however, the role of altered NCAPG2 expression and its transcriptional regulatory function in cancer development remains mostly unknown. Here, for the first time we reported that NCAPG2 was evidently increased in non‐small cell lung cancer tissues compared to adjacent normal lung tissues. Clinicopathological data analysis showed that NCAPG2 overexpression was significantly correlated with lymph node metastasis and pathologic‐Tumour Nodes Metastasen stages, and was an independent prognostic factor in lung adenocarcinoma patients. Moreover, siRNA‐mediated knockdown of NCAPG2 could inhibit tumour cell growth of lung adenocarcinoma cells (A549 and H1299) in vitro and could significantly lead to cell cycle arrest in the G2 phase. Furthermore, we found that NCAPG2 silencing significantly decreased the expression levels of G2/M phase cell cycle‐related protein expressions (Cyclin B1, Cdc2) and increased the expression levels of p27 and p21 through Western blot analysis. Taken together, we demonstrated that increased NCAPG2 expression could regulate cell proliferation and identified as a poor prognostic biomarker in lung adenocarcinoma.

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The condensin component NCAPG2 regulates microtubule–kinetochore attachment through recruitment of Polo-like kinase 1 to kinetochores

Cited by 47 publications

References 57 publications

Core Pluripotency Factors Directly Regulate Metabolism in Embryonic Stem Cell to Maintain Pluripotency

Core Pluripotency Factors Directly Regulate Metabolism in Embryonic Stem Cell to Maintain Pluripotency

Conditional mutation of Smc5 in mouse embryonic stem cells perturbs condensin localization and mitotic progression

NCAPG2 promotes tumour proliferation by regulating G2/M phase and associates with poor prognosis in lung adenocarcinoma

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