• 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.

• Journal of Life Science
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• v.11 no.4
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• pp.362-370
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• 2001

Regulation of cell proliferation is a complex process involving the regulated expression and /or modification of discrete gene products. which control transition between different stages of the cycle. The purpose of this short review is to provide an overview of somatic cell cycle events and their controls. Cycline have appeared as major positive regulators in this network, because their association to the cyclin-dependent kinases(Cdks) allows the subsequent activation on the Cdk/cyclin complexes and their catalatic activity. In mammalian cells, early to mid G1 progression and late G1 progression leading to S phase entry are directed by D-type cyclins-Cdk4, 6 and cyclin E-Cdk 2 both of which can phosphorylate the retinoblastoma protein (pRB). pRB is a transcriptional repressor which, in its unphosphorylated state, binds to members of the E2F transcription factor family and blocks E2F-dependent transcription of genes controlling the G1 to S phase transition an subsequent DNA synthesis. Cyclin A is produced in late G1 and expressed during S and G2 phae, and expression of B-type cyclins is typically maximal during the G2 to M phase transition and it controls the passage through M phase. They primarily associate with the activate Cdk2, and Cdc2, respectively. On the other hand, the Cdk inhibitors negatively control the activity of C아/cyclin complex by coordinating internal and/or external signals and impending proliferation at several key checkpoints. These current and further findings will provide novel approaches to understanding and treating major diseases.

• Molecules and Cells
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• v.39 no.9
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• pp.699-704
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• 2016

Developmentally regulated GTP-binding protein 2 (DRG2) plays an important role in cell growth. Here we explored the linkage between DRG2 and G2/M phase checkpoint function in cell cycle progression. We observed that knockdown of DRG2 in HeLa cells affected growth in a wound-healing assay, and tumorigenicity in nude mice xenografts. Flow cytometry assays and [$^3H$] incorporation assays indicated that G2/M phase arrest was responsible for the decreased proliferation of these cells. Knockdown of DRG2 elicited down-regulation of the major mitotic promoting factor, the cyclin B1/Cdk1 complex, but upregulation of the cell cycle arresting proteins, Wee1, Myt1, and p21. These findings identify a novel role of DRG2 in G2/M progression.

• Journal of Life Science
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• v.19 no.1
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• pp.1-8
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• 2009

In this paper, to elucidate the further mechanisms of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced growth arrest, we investigated the effect of MNNG on cell cycle and proliferation in U937 cells, a p53-null human myeloid leukemia cell line. It was found that MNNG causes an arrest at the G2/M phase of the cell cycle and induces apoptosis, which is closely correlated to inhibition of cyclin B1 and cyelin-dependent kinase (Cdk) 2-associated kinase activities. MNNG treatment in. creased protein and mRNA levels of the Cdk inhibitor p21(WAF1/CIP1), and activated the reporter construct of a p21 promoter. By using p21 promoter deletion constructs, the MNNG-responsive element was mapped to a region between 113 and 61 relative to the transcription start site. These data indicate that in U937 cells MNNG can circumvent the loss of wild-type p53 function and induce critical downstream regulatory events leading to transcriptional activation of p21. Present results indicate that the p53-independent up-regulation of p21 by MNNG is likely responsible for the inhibition of cyclin/Cdk complex kinase activity rather than the down-regulation of cyclins and Cdks expression. These novel phenomena have not been previously described and provide important new insights into the possible biological effects of MNNG.

• KSBB Journal
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• v.30 no.4
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• pp.175-181
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• 2015

Cells proliferate via repeating process that growth and division. This process is G1, S, G2 and M four phases consists. Monitoring the progression of the cell cycle is a specific step that to be a continuous process is repeated to adjust the start of the next step. At this time, this process is called a Checkpoint. Currently, there are three known checkpoints that G1-S phase, G2-M phase, and the M phase. In this study, we confirmed that cell cycle arrest effects by ethanol extracts of Artemisia annua Linne (AAE) in Hep3B liver cancer cells. AAE was regulated proteins which involved in cell cycle such as pAkt, pMDM2, p53, p21, pCDK2 (T14/Y15). AAE induced cell cycle arrest in G1 checkpoint through phosphorylation of CDK2. Akt and p53 upstream is inhibited by AAE and p53 activated by non-activated pMDM2, p53 inhibitor. Thereby, activated p53 is transcript to p21 and activated p21 protein is combined with Cyclin E-pCDK2 complex. Therefore, we confirmed that AAE-induced cell cycle arrest was occurred by p21-Cyclin E-pCDK2 complex by inhibition of pAkt signal. Because of this cell cycle can't pass to S phase from G1 phase.

• Journal of Life Science
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• v.25 no.10
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• pp.1184-1195
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• 2015

The zebrafish is an emerging vertebrate model organism in reproductive biology. The oocyte maturation of zebrafish is triggered by maturation inducing hormone (MIH, 17α,20β-Dihydroxy-4-pregnen-3-one). In almost all animals, the oocyte maturation is governed by activation of pre-MPF which consists of cyclinB and inactive Cdk1. In the oocyte of Xenopus and mice, the activity of Cdk1 is regulated in two ways, one is the interaction with cyclinB and the other is phosphorylation/dephosphorylation of T14/Y15 residues on the Cdk1 by Wee1 and Cdc25. Unlike Xenopus and mice that have a sufficient amount of pre-MPF, pre-MPF is absent in GV oocyte of most teleost including zebrafish. Therefore, the activation of MPF during zebrafish oocyte maturation might totally depend on de novo synthesis of cyclinB proteins. It is reported that the translation of maternal mRNA is regulated by combination of several RNA binding proteins such as CPEB, Dazl, Pum1/Pum2, and insulin-like growth factor2 mRNA-binding protein 3 in the zebrafish oocytes. However, the definitive mechanism of these proteins to regulate the translation of stored maternal mRNAs remains to be elucidated. Therefore, the investigation of the maturation process of the zebrafish oocyte will provide new information that can help identify the role of translational control in early vertebrate oocyte maturation.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1299-1308
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• 2016

Our previous studies clearly demonstrated that a combination of WP 631 and Epo B has higher activity against ovarian cancer cells than either of these compounds used separately. In order to fully understand the exact mechanism of action in combination, we assessed effects on the cell cycle of SKOV-3 cells. We evaluated three control points essential for WP 631 and Epo B action to determine which cell cycle-regulating proteins (CDK1/cyclin B complex, EpCAM or HMGB1) mediate activity. The effects of the drug on the cell cycle were measured based on the nuclear DNA content using flow cytometry. Expression of cell cycle-regulating genes was analyzed using real-time PCR. It was discovered that WP 631, at the tested concentration, did not affect the SKOV-3 cell cycle. Epo B caused significant G2/M arrest, whereas the drug combination induced stronger apoptosis and lower mitotic arrest than Epo B alone. This is very important information from the point of view of the fight against cancer, as, while mitotic arrest in Epo B-treated cells could be overcame after DNA damage repair, apoptosis which occurs after mitotic slippage in combination-treated cells is irreversible. It clearly explains the higher activity of the drug combination in comparison to Epo B alone. Epo B acts via the CDK1/cyclin B complex and has the ability to inhibit CDK1, which may be a promising strategy for ovarian cancer treatment in the future. The drug combination diminishes EpCAM and HMGB1 expression to a greater degree than either WP 631 and Epo B alone. Owing to the fact that the high expression of these two proteins is a poor prognostic factor for ovarian cancer, a decrease in their expression, observed in our studies, may result in improved efficacy of cancer therapy. The presented findings show that the combination of WP 631 and Epo B is a better therapeutic option than either of these drugs alone.

• Journal of Dental Rehabilitation and Applied Science
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• v.38 no.3
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• pp.150-161
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• 2022

Purpose: To determine the effects of the microgroove-fibronectin complex surface on the expression of various genes related to cellular activity in human gingival fibroblasts. Materials and Methods: Smooth titanium specimens (NE0), acid-treated titanium specimens (E0), microgroove and acid-treated titanium specimens (E60/10), fibronectin-fixed smooth titanium specimens (NE0FN), acid-treated and fibronectin-immobilized titanium specimens (E0FN), and microgroove and acid-treated titanium specimens immobilized with fibronectin (E60/10FN) were prepared. Real-time polymerase chain reaction experiments were conducted on 44 genes related to cell behavior of human gingival fibroblasts. Results: Adhesion and proliferation of human gingival fibroblast on microgroove-fibronectin complex titanium were activated through four types of signaling pathway. Integrin α5, Integrin β1, Integrin β3, Talin-2, which belong to the focal adhesion pathway, AKT1, AKT2, NF-κB, which belong to the PI3K-AKT signaling pathway, MEK2, ERK1, ERK2, which belong to the MAPK signaling pathway, and Cyclin D1, CDK4, CDK6 genes belonging to the cell cycle signaling pathway were upregulated on the microgroove-fibronectin complex titanium surface (E60/10FN). Conclusion: The microgroove-fibronectin complex titanium surface can up-regulate various genes involved in cell behavior.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6649-6655
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• 2014

Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.