• BMB Reports
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• v.51 no.6
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• pp.261-262
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• 2018

Aurora B is an important kinase involved in dynamic cellular events in mitosis. Aurora B activity is controlled by several post-translational modifications (PTMs). Among them, E3 ubiquitin ligase-mediated ubiquitination plays crucial roles in controlling the relocation and degradation of Aurora B. Aurora B, ubiquitinated by different E3 ligases, moves to the exact site for its mitotic function during metaphase-anaphase transition and is then degraded for cell cycle progression at the end of mitosis. However, how the stability of Aurora B is maintained until its degradation has been poorly understood. Recently, we have found that USP35 acts as a deubiquitinating enzyme (DUB) for Aurora B and affects its stability during cell division, thus being involved in the regulation of mitosis. In this review, we discuss the USP35-mediated deubiquitination of Aurora B and the regulation of mitotic progression by USP35.

• Bulletin of the Korean Chemical Society
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• v.33 no.3
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• pp.869-880
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• 2012

Identification of the selective chemical features for Aurora-B inhibitors gained much attraction in drug discovery for the treatment of cancer. Hence to identify the Aurora-B critical features various techniques were utilized such as pharmacophore generation, virtual screening, homology modeling, molecular dynamics, and docking. Top ten hypotheses were generated for Aurora-B and Aurora-A. Among ten hypotheses, HypoB1 and HypoA1 were selected as a best hypothesis for Aurora-B and Aurora-A based on cluster analysis and ranking score, respectively. Test set result revealed that ring aromatic (RA) group in HypoB1 plays an essential role in differentiates Aurora-B from Aurora-A inhibitors. Hence, HypoB1 used as 3D query in virtual screening of databases and the hits were sorted out by applying drug-like properties and molecular docking. The molecular docking result revealed that 15 hits have shown strong hydrogen bond interactions with Ala157, Glu155, and Lys106. Hence, we proposed that HypoB1 might be a reasonable hypothesis to retrieve the structurally diverse and selective leads from various databases to inhibit Aurora-B.

• Reproductive and Developmental Biology
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• v.35 no.4
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• pp.499-502
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• 2011

Aurora A kinase is a mitotic serine/threonine kinase whose proposed functions include the maturation of centrosomes, G2/M transition, alignment of chromosomes at metaphase, and cytokinesis. In this study, we investigated the effect of MLN8237, an aurora A kinase inhibitor, on the postovulatory aging of oocytes based on the frequency of oocyte fragmentation, cdk1 kinase activity, and cyclin B degradation. The fragmentation of ovulated oocytes during prolonged culture was inhibited by treatment with MLN8237 in a concentration-dependent manner. The frequency of fragmented oocytes was significantly lower in oocytes treated with 2 ${\mu}M$ MLN8237 (13%) than in control oocytes (64%) after two days of culture. Most of the control (non-fragmented) oocytes (91%) were activated after two days of culture. In comparison, only 22% of the MLN8237-treated oocytes were activated; the rest of the oocytes (78%) were still in metaphase with an abnormal spindle and dispersed chromosomes. Next, cdk1 activity and the level of cyclin B were examined. The level of cyclin B and cdk1 activity in MLN8237-treated oocytes were nearly equal to those in control oocytes. Our results indicate that MLN8237 inhibited the fragmentation of ovulated oocytes during prolonged culture, although it blocked the spontaneous decrease in activity of cdk1 and degradation of cyclin B. This mechanism of inhibition is different from that in oocytes treated with nocodazole, which have high levels of cdk1 activity and cyclin B.

• BMB Reports
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• v.55 no.2
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• pp.87-91
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• 2022

Aurora kinase is a family of serine/threonine kinases intimately associated with mitotic progression and the development of human cancers. Studies have shown that aurora kinases are important for the protein kinase C (PKC)-induced invasion of colon cancer cells. Recent studies have shown that aurora kinase A promotes distant metastasis by inducing epithelial-to-mesenchymal transition (EMT) in colon cancer cells. However, the role of aurora kinase A in colon cancer metastasis remains unclear. In this study, we investigated the effects of aurora kinase A on PKC-induced cell invasion, migration, and EMT in human SW480 colon cancer cells. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) changed the expression levels of EMT markers, increasing α-SMA, vimentin, and MMP-9 expression and decreasing E-cadherin expression, with changes in cell morphology. TPA treatment induced EMT in a PKC-dependent manner. Moreover, the inhibition of aurora kinase A by siRNAs and inhibitors (reversine and VX-680) suppressed TPA-induced cell invasion, migration, and EMT in SW480 human colon cells. Inhibition of aurora kinase A blocked TPA-induced vimentin and MMP-9 expression, and decreased E-cadherin expression. Furthermore, the knockdown of aurora kinase A decreased the transcriptional activity of NF-κB and AP-1 in PKC-stimulated SW480 cells. These findings indicate that aurora kinase A induces migration and invasion by inducing EMT in SW480 colon cancer cells. To the best of our knowledge, this is the first study that showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.481-488
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• 2022

Background: Although the tumor-suppressive effects of ginsenosides in cell cycle have been well established, their pharmacological properties in mitosis have not been clarified yet. The chromosomal instability resulting from dysregulated mitotic processes is usually increased in cancer. In this study, we aimed to investigate the anticancer effects of ginsenoside Rg1 on mitotic progression in cancer. Materials and methods: Cancer cells were treated with ginsenoside Rg1 and their morphology and intensity of different protein were analyzed using immunofluorescence microscopy. The level of proteins in chromosomes was compared through chromosomal fractionation and Western blot analyses. The location and intensity of proteins in the chromosome were confirmed through immunostaining of mitotic chromosome after spreading. The colony formation assays were conducted using various cancer cell lines. Results: Ginsenoside Rg1 reduced cancer cell proliferation in some cancers through inducing mitotic arrest. Mechanistically, it inhibits the phosphorylation of histone H3 Thr3 (H3T3ph) mediated by Haspin kinase and concomitant recruitment of chromosomal passenger complex (CPC) to the centromere. Depletion of Aurora B at the centromere led to abnormal centromere integrity and spindle dynamics, thereby causing mitotic defects, such as increase in the width of the metaphase plate and spindle instability, resulting in delayed mitotic progression and cancer cell proliferation. Conclusion: Ginsenoside Rg1 reduces the level of Aurora B at the centromere via perturbing Haspin kinase activity and concurrent H3T3ph. Therefore, ginsenoside Rg1 suppresses cancer cell proliferation through impeding mitotic processes, such as chromosome alignment and spindle dynamics, upon depletion of Aurora B from the centromere.

• The Journal of the Korea institute of electronic communication sciences
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• v.8 no.4
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• pp.555-560
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• 2013

This paper first proposes a classification algorithm which detects a voiced, unvoiced, and silence signal using distance measure, logarithm power and root mean square methods at each frame, then a spectrum subtraction algorithm based on a subband filter. The proposed algorithm subtracts spectrums of white noise and street noise from noisy signal based on the subband filter at each frame. In this experiment, experimental results of the proposed spectrum subtraction algorithm demonstrate using the speech and noise data of Aurora-2 database. Based on measuring the speech-to-noise ratio (SNR), experiments confirm that the proposed algorithm is effective for the speech by contaminated the noise. From the experiments, the improvement in the output SNR values was approximately 2.1 dB and 1.91 dB better for white noise and street noise, respectively.

• BMB Reports
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• v.46 no.6
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• pp.289-294
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• 2013

To maintain cellular homeostasis against the demands of the extracellular environment, a precise regulation of kinases and phosphatases is essential. In cell cycle regulation mechanisms, activation of the cyclin-dependent kinase (CDK1) and cyclin B complex (CDK1:cyclin B) causes a remarkable change in protein phosphorylation. Activation of CDK1:cyclin B is regulated by two auto-amplification loops-CDK1:cyclin B activates Cdc25, its own activating phosphatase, and inhibits Wee1, its own inhibiting kinase. Recent biological evidence has revealed that the inhibition of its counteracting phosphatase activity also occurs, and it is parallel to CDK1:cyclin B activation during mitosis. Phosphatase regulation of mitotic kinases and their substrates is essential to ensure that the progression of the cell cycle is ordered. Outlining how the mutual control of kinases and phosphatases governs the localization and timing of cell division will give us a new understanding about cell cycle regulation.

• Molecules and Cells
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• v.41 no.5
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• pp.444-453
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• 2018

Aberrations in histone modifications are being studied in mixed-lineage leukemia (MLL)-AF9-driven acute myeloid leukemia (AML). In this study, we focused on the regulation of the differentiation of the MLL-AF9 type AML cell line THP-1. We observed that, upon phorbol 12-myristate 13-acetate (PMA) treatment, THP-1 cells differentiated into monocytes by down-regulating Aurora kinase A (AURKA), resulting in a reduction in H3S10 phosphorylation. We revealed that the AURKA inhibitor alisertib accelerates the expression of the H3K27 demethylase KDM6B, thereby dissociating AURKA and YY1 from the KDM6B promoter region. Using Flow cytometry, we found that alisertib induces THP-1 differentiation into monocytes. Furthermore, we found that treatment with the KDM6B inhibitor GSK-J4 perturbed the PMA-mediated differentiation of THP-1 cells. Thus, we discovered the mechanism of AURKA-KDM6B signaling that controls the differentiation of THP-1 cells, which has implications for biotherapy for leukemia.

• The Journal of the Acoustical Society of Korea
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• v.37 no.6
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• pp.506-511
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• 2018

This paper proposes an GMM(Gaussian Mixture Model)-DNN(Deep Neural Network) hybrid-based feature compensation method for effective speech recognition in noisy environments. In the proposed algorithm, the posterior probability for the conventional GMM-based feature compensation method is calculated using DNN. The experimental results using the Aurora 2.0 framework and database demonstrate that the proposed GMM-DNN hybrid-based feature compensation method shows more effective in Known and Unknown noisy environments compared to the GMM-based method. In particular, the experiments of the Unknown environments show 9.13 % of relative improvement in the average of WER (Word Error Rate) and considerable improvements in lower SNR (Signal to Noise Ratio) conditions such as 0 and 5 dB SNR.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.734-743
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• 2021

Background: The underlying mechanisms of the potential tumor-suppressive effects of ginsenoside Rh2 are complex. N6-methyladenosine (m6A) RNA methylation is usually dysregulated in cancer. This study explored the regulatory effect of ginsenoside Rh2 on m6A RNA methylation in cancer. Methods: m6A RNA quantification and gene-specific m6A RIP-qPCR assays were applied to assess total and gene-specific m6A RNA levels. Co-immunoprecipitation, fractionation western blotting, and immunofluorescence staining were performed to detect protein interactions and distribution. QRT-PCR, dual-luciferase, and ChIP-qPCR assays were conducted to check the transcriptional regulation. Results: Ginsenoside Rh2 reduces m6A RNA methylation and KIF26B expression in a dose-dependent manner in some cancers. KIF26B interacts with ZC3H13 and CBLL1 in the cytoplasm of cancer cells and enhances their nuclear distribution. KIF26B inhibition reduces m6A RNA methylation level in cancer cells. SRF bound to the KIF26B promoter and activated its transcription. SRF mRNA m6A abundance significantly decreased upon KIF26B silencing. SRF knockdown suppressed cancer cell proliferation and growth both in vitro and in vivo, the effect of which was partly rescued by KIF26B overexpression. Conclusion: ginsenoside Rh2 reduces m6A RNA methylation via downregulating KIF26B expression in some cancer cells. KIF26B elevates m6A RNA methylation via enhancing ZC3H13/CBLL1 nuclear localization. KIF26B-SRF forms a positive feedback loop facilitating tumor growth.