• The Journal of Korea Institute of Information, Electronics, and Communication Technology
• /
• v.1 no.2
• /
• pp.39-50
• /
• 2008

Developing computational methods for identifying cell cycle-regulated genes has been one of important topics in systems biology. Most of previous methods consider the periodic characteristics of expression signals to identify the cell cycle-regulated genes. However, we assume that cell cycle-regulated genes are relatively active having relatively many interactions with each other based on the underlying cellular network. Thus, we are motivated to apply the theory of multivariate phase synchronization to the cell cycle expression analysis. In this study, we apply the method known as "Self-Organizing Maps with statistical Phase Synchronization (SOMPS)", which is the combination of self-organizing map and multivariate phase synchronization, producing several subsets of genes that are expected to have interactions with each other in their subset (Kim, 2008). Our evaluation experiments show that the SOMPS algorithm is able to detect cell cycle-regulated genes as much as one of recently reported method that performs better than most existing methods.

• Mycobiology
• /
• v.51 no.5
• /
• pp.372-378
• /
• 2023

Lkh1, a LAMMER kinase homolog in the fission yeast Schizosaccharomyces pombe, acts as a negative regulator of filamentous growth and flocculation. It is also involved in the response to oxidative stress. The lkh1-deletion mutant displays slower cell growth, shorter cell size, and abnormal DNA content compared to the wild type. These phenotypes suggest that Lkh1 controls cell size and cell cycle progression. When we performed microarray analysis using the lkh1-deletion mutant, we found that only four of the up-regulated genes in the lkh1-deletion were associated with the cell cycle. Interestingly, all of these genes are regulated by the Mlu1 cell cycle box binding factor (MBF), which is a transcription complex responsible for regulating the expression of cell cycle genes during the G1/S phase. Transcription analyses of the MBF-dependent cell-cycle genes, including negative feedback regulators, confirmed the up-regulation of these genes by the deletion of lkh1. Pull-down assay confirmed the interaction between Lkh1 and Yox1, which is a negative feedback regulator of MBF. This result supports the involvement of LAMMER kinase in cell cycle regulation by modulating MBF activity. In vitro kinase assay and NetPhosK 2.0 analysis with the Yox1T40,41A mutant allele revealed that T40 and T41 residues are the phosphorylation sites mediated by Lkh1. These sites affect the G1/S cell cycle progression of fission yeast by modulating the activity of the MBF complex.

• The Journal of Korean Medicine
• /
• v.20 no.2
• /
• pp.88-97
• /
• 1999

To characterize the effects of Gilgyung-Tang(GGT) on cellular proliferation and viability of normal lung fibroblast cells, we examined the cell cycle progression and cell cycle-related gene expression in T3891 using a flow cytometry and a quantitative RT-PCR analysis. 1. The significant surpression effect of cellular proliferations of GGT was observed in proportion to a certain concentration and time. 2. GGT was identified to induce apoptotic death of damaged cells by treatment with a DNA-damage agent and etoposide, while it stimulated the recovery of cellular viability of normal cells. 3 The significant reductions of mRNA expression of PCAN, c-Fos treated by GGT were observed. 4. The significant inductions of mRNA expression of p53, CDKN1. Gadd45 treated by GGT were observed. 5. The apoptosis caused by the reduction of Bcl-2 genes was significant and the Bax genes were increased. but the amount of Fas genes were not changed. These results strongly suggest that GGT triggers arrest of the cell cycle at G1 phase, and thus causes an inhibition of cellular proliferation of human normal lung cells through the transcriptional up-regulation of cell cycle inhibitory genes and down-regulation of induction of cell cycle stimulating genes respectably.

• Molecular & Cellular Toxicology
• /
• v.2 no.3
• /
• pp.159-165
• /
• 2006

To determine the anticancer effect of D-amygdalin (D-mandelinitrole-${\beta}$-D-gentiobioside) in human chronic myeloid leukemia cells K562, we profiled the gene expression between amygdalin treatment and control groups. Through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, the cytotoxicity of D-amygdalin was $57.79{\pm}1.83%$ at the concentration of 5 mg/mL for 24 h. We performed cDNA microarray analysis and compared the gene expression profiles between D-amygdalin (5 mg/mL, 24 h) treatment and control groups. Among the genes changed by D-amygdalin, we paid attention to cell cycle-related genes, and particularly cell cycle regulator genes; because arrest of cell cycle processing was ideal tactic in remedy for cancer. In our data, expressions of cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B), ataxia telangiectasia mutated (includes complementation groups A, C, and D) (ATM), cyclin-dependent kinase inhibitor 1C (p57, Kip2) (CDKN1C), and CHK1 checkpoint homolog (CHEK1, formally known as CHK1) were increased, while expressions of cyclin-dependent kinase 2 (CDK2), cell division cycle 25A (CDC25A), and cyclin E1 (CCNE1) were decreased. The pattern of these gene expressions were confirmed through RT-PCR. Our results showed that D-amygdalin might control cell cycle regulator genes and arrest S phase of cell cycle in K562 cells as the useful anticancer drug.

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.13 no.9
• /
• pp.3952-3961
• /
• 2012

Developing computational methods for identifying cell cycle-regulated genes has been one of important topics in systems biology. Most of previous methods consider the periodic characteristics of expression signals to identify the cell cycle-regulated genes. However, we assume that cell cycle-regulated genes are relatively active having relatively many interactions with each other based on the underlying cellular network. Thus, we are motivated to apply the theory of multivariate phase synchronization to the cell cycle expression analysis. In this study, we apply the method known as "Self-Organizing Maps with statistical Phase Synchronization (SOMPS)", which is the combination of self-organizing map and multivariate phase synchronization, producing several subsets of genes that are expected to have interactions with each other in their subset (Kim, 2008). Our evaluation experiments show that the SOMPS algorithm is able to detect cell cycle-regulated genes as much as one of recently reported method that performs better than most existing methods.

• Journal of Life Science
• /
• v.16 no.5
• /
• pp.828-833
• /
• 2006

Maize (Zea mays L.) pistil cell death and stamen cell arrest are pivotal process on the sex determination, which diverges from bisexual state of floral meristem to unisexual state in staminate or pistillate floret. We investigated the temporal and spatial distribution of cell cycle gene expression during maize sex determination. The positive regulatory genes of cell cycle, cyclin A, cyclin B, cyclin dependent kinase (CDK) and Mad2 were highly expressed in the developing pistil and stamen but the expression was disappeared in the dying pistil and arresting stamens. In contrast, the negative regulatory genes of cell cycle, Wee1 and CDK inhibitor (CKI) were expressed in the arresting stamens in the wild-type ear and tasselseed2 mutant tassel, however, these genes were not detected in dying pistil although the cyclin B gene expression was disappeared. These results suggest that both the pistil cell death and stamen cell arrest process in maize sex determination are involved in cell cycle regulation, but the different expression patterns of negative regulatory cell cycle genes in the arresting stamens and aborting pistils suggest that the two processes may have distinctive modes of action.

• Parasites, Hosts and Diseases
• /
• v.57 no.2
• /
• pp.185-189
• /
• 2019

To identify the component(s) involved in cell cycle control in the protozoan Giardia lamblia, cells arrested at the G1/S- or G2-phase by treatment with nocodazole and aphidicolin were prepared from the synchronized cell cultures. RNA-sequencing analysis of the 2 stages of Giardia cell cycle identified several cell cycle genes that were up-regulated at the G2-phase. Transcriptome analysis of cells in 2 distinct cell cycle stages of G. lamblia confirmed previously reported components of cell cycle (PcnA, cyclin B, and CDK) and identified additional cell cycle components (NEKs, Mad2, spindle pole protein, and CDC14A). This result indicates that the cell cycle machinery operates in this protozoan, one of the earliest diverging eukaryotic lineages.

• BMB Reports
• /
• v.38 no.4
• /
• pp.447-456
• /
• 2005

TNF-$\alpha$ plays a pivotal role in inflammation processes which are mainly regulated by endothelial cells. While TNF-$\alpha$ induces apoptosis of several cell types like tumor cells, endothelial cells are resistant to TNFa mediated cell death. The cytotoxic effects of TNF-$\alpha$ on most cells are only evident if RNA or protein synthesis is inhibited, suggesting that de novo RNA or protein synthesis protect cells from TNF-$\alpha$ cytotoxicity, presumably by NF-${\kappa}B$ mediated induction of protective genes. However, the cytoprotective genes involved in NF-${\kappa}B$ dependent endothelial cell survival have not been sufficiently identified. In the present study, the suppression subtractive hybridization (SSH) method was employed to identify rarely transcribed TNF-$\alpha$ inducible genes in human arterial endothelial cells related to cell survival and cell cycle. The TNF-$\alpha$-induced expression of the RNA binding protein $p54^{nrb}$ and the 14-3-3 protein HS1 as shown here for the first time may contribute to the TNF-$\alpha$ mediated cell protection of endothelial cells. These genes have been shown to play pivotal roles in cell survival and cell cycle control in different experimental settings. The concerted expression of these genes together with other genes related to cell protection and cell cycle like DnaJ, $p21^{cip1}$ and the ubiquitin activating enzyme E1 demonstrates the identification of new genes in the context of TNF-$\alpha$ induced gene expression patterns mediating the prosurvival effect of TNF-$\alpha$ in endothelial cells.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
• /
• v.7 no.1
• /
• pp.1-18
• /
• 2001

Objective: This experimental study was carried out to evaluate the effects of Saussurea Radix and Plantaginis Herba on cellular viability, proliferation, apoptosis and expression of the cell cycle-related genes in cultured gastric cancer cells. Method :MTT assay for analysis of cellular toxicity and the effect on suppression of cellular viability, $[^{3}H]$ thymidine incorporation assay for evaluation of the effect on suppression of DNA replication, tryphan blue exclusion assay for measurement of induction of apoptosis and Quantitative RT-PCR for analysis of the effects on expression of cell cycle or apoptosis-related genes were performed. Results: Antitumor activity of Saussurea Radix associated with inhibition of cell cycle progression and promotion of apoptosis caused by transcriptional regulation of p53, p21/Wafl and the other related genes was observed.

• Journal of Microbiology
• /
• v.39 no.1
• /
• pp.74-78
• /
• 2001

The transcription of the chitin synthase genes (chss) was cell cycle-regulated in Aspergillus nidulans and the expression pattern was classified into two groups. Group one, containing chsA and chsC, showed decreasing transcription level upon entry into the S-phase and no further variation during the remainder of the cell cycle. However, group two, containing chsB, chsD, and csmA showed a sharp decrease of mRNA level upon entry into the G2-phase and an increase during the M-phase. Our results suggested that the chss, belonging to same group with the similar expression pattern during the cell cycle are functionally linked and that chsD may play a role in hyphal growth and development in A. nidulans.