• Journal of Life Science
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• v.29 no.6
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• pp.645-652
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• 2019

Non-small cell lung cancer (NSCLC) has the infamous distinction of being the leading cause of global cancer-related death over the past decade, and novel molecular targets are urgently required to change this status. We previously conducted a microarray analysis to investigate the association of transcription factor activating enhancer-binding protein 2C (TFAP2C) with NSCLC and revealed its oncogenic roles in NSCLC development. In this study, to identify new biomarkers for NSCLC, we focused on several oncogenes from the microarray analysis that are transcriptionally regulated by TFAP2C. Here, the cell division cycle 20 (CDC20) and tribbles pseudokinase 3 (TRIB3) were subsequently found as potential potent oncogenes as they are positively regulated by TFAP2C. The results showed that the mRNA and protein levels of CDC20 and TRIB3 were down-regulated in two NSCLC cell lines (NCI-H292 and NCI-H838), which were treated with TFAP2C siRNA, and that the overexpression of either CDC20 or TRIB3 was responsible for promoting cell viability in both NSCLC cell lines. In addition, apoptotic levels of NCI-H292 and NCI-H838 cells treated with TFAP2C siRNA were found to be suppressed by the overexpression of either CDC20 or TRIB3. Together, these results suggest that CDC20 and TRIB3 are positively related to NSCLC tumorigenesis and that they should be considered as potential prognostic markers for developing an NSCLC therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.931-935
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• 2012

Cdc25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of Cdc25B in renal cell carcinomas remains unknown. To shed light on influence on renal cell carcinogenesis and subsequent progression, Cdc25B expression was examined by real-time RT-PCR and western blotting in renal cell carcinoma and normal tissues. 65 kDa Cdc25B expression was higher in carcinomas than in the adjacent normal tissues (P<0.05), positive correlations being noted with clinical stage and histopathologic grade (P<0.05). To additionally investigate the role of Cdc25B alteration in the development of renal cell carcinoma, Cdc25B siRNA was used to knockdown the expression of Cdc25B. Down-regulation resulted in slower growth, more G2/M cells, weaker capacity for migration and invasion, and induction of apoptosis in 769-P transfectants. Reduction of 14-3-3 protein expression appeared related to Cdc25B knockdown. These findings suggest an important role of Cdc25B in renal cell carcinoma development and provide a rationale for investigation of Cdc2B-based gene therapy.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.71.1-71.1
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• 2003

We show that Cdc6, an essential initiation factor for DNA replication, undergoes caspase-3-mediated cleavage in the early stages of apoptosis in HeLa cells and SK-HEP-1 cells induced by etoposide, paclitaxel, ginsenoside Rh2, or TRAIL. The cleavage occurs at the SEVD$\^$442//G motif and generates an N-terminal truncated Cdc6 fragment (p49-tCdc6) that lacks the carboxy-terminal nuclear export sequence (NES). Cdc6 is known to be phosphorylated by cyclin A-Cyclin A-dependent kinase 2 (Cdk2), an event that promotes its exit from the nucleus and probably blocks it from initiating inappropriate DNA replication. (omitted)

• Molecules and Cells
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• v.41 no.5
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• pp.436-443
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• 2018

The actin cytoskeleton plays a key role in the entry of mitosis as well as in cytokinesis. In a previous study, we showed that actin disruption delays mitotic entry at G2/M by sustained activation of extracellular signal-related kinase 1/2 (ERK1/2) in primary cells but not in transformed cancer cell lines. Here, we examined the mechanism of cell cycle delay at G2/M by actin dysfunction in IMR-90 normal human fibroblasts. We observed that de-polymerization of actin with cytochalasin D (CD) constitutively activated ribosomal S6 kinase (RSK) and induced inhibitory phosphorylation of Cdc2 (Tyr 15) in IMR-90 cells. In the presence of an actin defect in IMR-90 cells, activating phosphorylation of Wee1 kinase (Ser 642) and inhibitory phosphorylation of Cdc25C (Ser 216) was also maintained. However, when kinase-dead RSK (DN-RSK) was overexpressed, we observed sustained activation of ERK1/2, but no delay in the G2/M transition, demonstrating that RSK functions downstream of ERK in cell cycle delay by actin dysfunction. In DN-RSK overexpressing IMR-90 cells treated with CD, phosphorylation of Cdc25C (Ser 216) was blocked and phosphorylation of Cdc2 (Tyr 15) was decreased, but the phosphorylation of Wee1 (Ser 642) was maintained, demonstrating that RSK directly controls phosphorylation of Cdc25C (Ser 216), but not the activity of Wee1. These results strongly suggest that actin dysfunction in primary cells activates ERK1/2 to inhibit Cdc2, delaying the cell cycle at G2/M by activating downstream RSK, which phosphorylates and blocks Cdc25C, and by directly activating Wee1.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.427-436
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• 2023

Mitotic arrest deficient 2 like 2 (Mad2L2, also known as Mad2B), the human homologue of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares high sequence homology with Mad2, the mitotic checkpoint protein. Previously, we demonstrated the involvement of Mad2B in the cisplatin-induced DNA damage response. In this study, we extend our findings to show that Mad2B is recruited to sites of DNA damage in human cancer cells in response to cisplatin treatment. We found that in undamaged cells, Mad2B exists in a complex with Polζ-Rev1 and the APC/C subunit Cdc27. Following cisplatin-induced DNA damage, we observed an increase in the recruitment of Mad2B and Cdc20 (the activators of the APC/C), to the complex. The involvement of Mad2B-Cdc20-APC/C during DNA damage has not been reported before and suggests that the APC/C is activated following cisplatin-induced DNA damage. Using an in vitro ubiquitination assay, our data confirmed Mad2B-dependent activation of APC/C in cisplatin-treated cells. Mad2B may act as an accelerator for APC/C activation during DNA damage response. Our data strongly suggest a role for Mad2B-APC/C-Cdc20 in the ubiquitination of proteins involved in the DNA damage response.

• Animal cells and systems
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• v.10 no.1
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• pp.1-6
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• 2006

Previous studies showed that Cdc7 kinase of Schizosaccharomyces pombe phosphorylated the minichromosome maintenance (Mcm) complex efficiently in the presence of spMcm10 protein. The biochemical properties of the phosphorylated Mcm complexes were examined to understand the activation mechanism of the Mcm complex by Cdc7 kinase. The phosphorylation of Mcm complex in the presence of spMcm10 by Cdc7 kinase did not affect the stability of the Mcm complex containing all six subunits, and the changes in the sedimentation properties were not observed after the phosphorylation. The reconstitution of the Mcm complex using the purified proteins showed that the phosphorylation of Mcm2 proteins did not affect the interactions between Mcm proteins. The phosphorylation of the Mcm2-7 complex at the same condition also did not activate the other biochemical activities such as DNA helicase and single stranded (ss) DNA binding activities. On the other hand, spMcm10 protein that was used for the stimulation of Mcm phosphorylation showed single stranded DNA binding activity, and inhibited the DNA helicase activity of the Mcm4/6/7 complex. These inhibitory effects were reduced by the addition of Cdc7 kinase, suggesting that the phosphorylation by Cdc7 kinase decreased the interactions between spMcm10 and the Mcm complex. Taken together, these results suggested that the phosphorylation by Cdc7 kinase alone is not sufficient for the remodeling and the activation of the Mcm complex, and the additional factors or the phosphorylations might be required for the activation of the Mcm complex.

• Journal of Korean Dental Hygiene Science
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• v.6 no.1
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• pp.27-36
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• 2023

Background: The purpose of the study was to investigate the level of infection control and prevention awareness among dental practitioners in Korea based on the infection control and prevention guidelines of the Centers for Disease Control and Prevention (CDC) in the United States. Methods: A survey was created on 'Standard and Education on CDC Infection Control Standards', 'Matters related to CDC Infection Control Prevention', and 'Characteristics of Research Subjects and Infection Control Characteristics' based on the CDC Dental Infection Control List.' A total of 222 surveys were conducted and used for frequency and cross-tabulation analyses. Results: Most research participants worked at university or general hospitals, and 93.7% had received infection prevention education within the past year. The average awareness of the CDC dental infection control standards and education was 77.2 %, which was higher than previous research results. Preventive awareness was 71.5% on average, and there was a statistically significant difference in preventive awareness between the certified and non-certified evaluation groups (p<0.001). Conclusion: The participants of this study showed a higher awareness of infection control standards, education, and prevention than those in previous studies. However, this was insufficient compared with the CDC dental infection control standard prevention guidelines. Therefore, government agencies and related organizations must establish systematic infection control systems.

• Journal of Life Science
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• v.32 no.2
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• pp.161-166
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• 2022

Mitosis is a process in which a replicated genome is distributed to two daughter cells, and it is necessary for cell survival and organismal development. During mitosis, the spindle assembly checkpoint (SAC) ensures faithful chromosome segregation by monitoring the kinetochore attachment to the mitotic spindle. Although the SAC mechanism has been extensively studied over the last 30 years, the mechanism by which a single unattached kinetochore activates the SAC remains unclear. The key components of the SAC are Mad1, Mad2, Mad3 (BubR1 in higher eukaryotes), Bub1, Bub3, and Cdc20, which are all required for SAC activation. An essential step for SAC activation is the formation of the Mad2 - Cdc20 complex in the unattached kinetochore, which is kinetically disfavored. Although the mechanism by which Mad2 and Cdc20 are recruited to unattached kinetochores is well-known, it is not clear how they form a complex. Recently, a key mechanism for the formation of the Mad2 - Cdc20 complex has been identified, which is catalyzed by an unattached kinetochore. This supports the evidence that a single unattached kinetochore can activate the SAC signaling. Herein, we discuss the known key mechanism for SAC activation, review the recent studies on SAC, and conclude how their discoveries improved the understanding of mitosis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5725-5730
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• 2013

Cancer patients often suffer from local tumor recurrence after radiation therapy. Cell cycling, an intricate sequence of events which guarantees high genomic fidelity, has been suggested to affect DNA damage responses and eventual radioresistant characteristics of cancer cells. Here, we established a radioresistant lung cancer cell line, A549R, by exposing the parental A549 cells to repeated ${\gamma}$-ray irradiation with a total dose of 60 Gy. The radiosensitivity of A549 and A549R was confirmed using colony formation assays. We then focused on examination of the cell cycle distribution between A549 and A549R and found that the proportion of cells in the radioresistant S phase increased, whereas that in the radiosensitive G1 phase decreased. When A549 and A549R cells were exposed to 4 Gy irradiation the total differences in cell cycle redistribution suggested that G2-M cell cycle arrest plays a predominant role in mediating radioresistance. In order to further explore the possible mechanisms behind the cell cycle related radioresistance, we examined the expression of Cdc25 proteins which orchestrate cell cycle transitions. The results showed that expression of Cdc25c increased accompanied by the decrease of Cdc25a and we proposed that the quantity of Cdc25c, rather than activated Cdc25c or Cdc25a, determines the radioresistance of cells.

• Molecules and Cells
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• v.27 no.3
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• pp.345-350
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• 2009

We previously reported that flavone induces embryonic lethality in Caenorhabditis elegans, which appeared to be the result of cell cycle arrest during early embryogenesis. To test this possibility, here we examined whether flavone inhibits the activity of a key cell cycle regulator, CDC-25.1 in C. elegans. A gain-of-function cdc-25.1 mutant, rr31, which exhibits extra cell divisions in intestinal cells, was used to test the inhibitory effects of flavone on CDC-25 activity. Flavone inhibited the extra cell divisions of intestinal cells in rr31, and modifications of flavone reduced the inhibitory effects. The inhibitory effects of flavone on CDC-25.1 were partly, if not completely, due to transcriptional repression.