• Title/Summary/Keyword: CDC

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Caspase-3-mediated cleavage of Cdc6 induces nuclear localization of truncated Cdc6 and apoptosis

  • Yim, Hyung-Shin;Jin, Ying-Hua;Park, Byoung-Duck;Lee, Seung-Ki
    • 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)

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Involvement of Cdc25c in Cell Cycle Alteration of a Radioresistant Lung Cancer Cell Line Established with Fractionated Ionizing Radiation

  • Li, Jie;Yang, Chun-Xu;Mei, Zi-Jie;Chen, Jing;Zhang, Shi-Min;Sun, Shao-Xing;Zhou, Fu-Xiang;Zhou, Yun-Feng;Xie, Cong-Hua
    • 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.

The Replicon Initiation Burst Released by Reoxygenation of Hypoxic T24 Cells is Accompanied by Changes of MCM2 and Cdc7

  • Martin, Leenus
    • BMB Reports
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    • v.40 no.5
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    • pp.805-813
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    • 2007
  • Although MCM2 is obviously important for the initiation of eukaryotic DNA replication, its role in $O_2$ dependent regulation of replicon initiation is poorly understood. In this report, I analysed the changes of MCM2 during the transition from hypoxically suppressed replicon initiation to the burst of initiation triggered by reoxygenation in T24 cells. A high level of chromatin bound and nucleosolic MCM2 was found under the hypoxic replicon arrest. In contrast low cytosolic MCM2 was noticed. Recovery of $O_2$ induced phosphorylation and diminution of chromatin bound MCM2, whereas cytosolic MCM2 increased. The level of chromatin bound Cdc7 did not change significantly upon reoxygenation. However, after reoxygenation, significant phosphorylation of Cdc7 and an increase of coimmunoprecipitation with its substrate (MCM2) were observed. This provides a hint that reoxygenation may promote the kinase activity of Cdc7. These changes might be the critical factors in $O_2$ dependent regulation of replicon initiation. Moreover, phosphorylation of Cdc7 by Cdk2 can be observed in vitro, but seems to fail to regulate the level of chromatin bound Cdc7 as well as the changes of MCM2 in response to reoxygenation of hypoxically suppressed cells.

TFAP2C Promotes Cell Proliferation by Upregulating CDC20 and TRIB3 in Non-small Cell Lung Cancer Cells (비소세포폐암 발달 과정에서 TFAP2C에 의해 발현되는 CDC20과 TRIB3의 원암유전자 기능에 관한 연구)

  • Kim, Dain;Do, Hyunhee;Kang, JiHoon;Youn, BuHyun;Kim, Wanyeon
    • 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.

Complement-dependent Cytotoxic Crossmatch for Prevention of Hyperacute Rejection in Canine Renal Allografts (개의 신장 동종 이식에서 초급성 거부반응의 예방을 위한 보체의존성 세포독성 DLA 플래스 I 교차 반응)

  • Ghil Heh Myung;Woo Heung-Myung
    • Journal of Veterinary Clinics
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    • v.22 no.4
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    • pp.322-327
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    • 2005
  • DLA class I complement-dependent cytotoxicity (CDC) cross-match method was established to control hyperacute rejections in organ transplantation. The aim of the present study is to investigate if DLA class 1 CDC corssmatch method is effective to prevent hyperacute rejections in canine renal allografts. Seven mongrel dogs of similar age and weight were used. Erythrocyte crossmatch was first performed and only the negatives were used. Among the same blood types, CDC cross-match was performed. Anti-dog serum, Hank's balanced salt solution(HBSS), and tile self-serum was used as a positive-, a negative-, and all auto-control respectively. After the reaction with class I complement, it was stained with eosin and scored by international cytotoxicity scoring system under inverted phase microscope. According to these results, kidneys oi CDC negatives among same blood types were cross-transplanted to observe the incidence of hyperacute rejections. One of four 1.2 B blood type dogs had autoantibodies. here were negative CDC results among each blood type, and also there were negative results between different blood types. Two pairs with the same blood types and negative CDC results underwent allo-transplantation each other. There were no hyperacute rejections. DLA cross-match method studied in this experiment for canine renal allograft can be effective to prevent hyperacute rejections. it may be applicable for the future studies of histocompatibility testing in canine renal allografts.

Actin Dysfunction Induces Cell Cycle Delay at G2/M with Sustained ERK and RSK Activation in IMR-90 Normal Human Fibroblasts

  • Shrestha, Deepmala;Choi, Daeun;Song, Kiwon
    • 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.

A Study on the Multi-Level Distribution Policy of High Demand Rate Goods. (수요율이 높은 제품의 다단계 분배정책에 관한 연구)

  • 유형근;김종수
    • Journal of Korean Society of Industrial and Systems Engineering
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    • v.17 no.31
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    • pp.59-72
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    • 1994
  • This paper deals with ordering policies of consumable goods which have large demand rates in a multi-level distribution system. The system we are concerned consists of one Central Distribution Center(CDC) and N non-identical Regional Distribution Centers(RDCs) which have different demand rates, minimum fillrates, leadtimes, etc. The customer demand on the RDC is stationary poisson and the RDCs demand on the CDC is superposition of Q-stage Erlang distributions. We approximate the RDCs and CDC demand distribution to nomal in order to enhance the efficiency of algorithm. The relevant costs include a fixed ordering cost and inventory holding cost, and backorder cost. The objective is to find a continuous-review ordering policy that minimizes the expected average costs under constraints of minimum fill rates of RDCs and maximum allowable mean delay of CDC. We developed an algorithm for determining the optimal ordering policies of the CDC and the RDCs. We verified and compared the performance of the algorithm through the simulation using the algorithm result as the input parameters.

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Bactericidal Activity of Normal and Cirrhotic Patients' Sera against Vibrio vulnificus (정상인 및 간경화환자 혈청의 Vibrio vulnificus에 대한 살균효과)

  • Rhee, Joon-Haeng;Chung, Sun-Sik
    • The Journal of the Korean Society for Microbiology
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    • v.21 no.1
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    • pp.121-126
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    • 1986
  • Bactericidal activity of normal and cirrhotic patients' sera against Vibrio vulnificus was investigated and compared each other as a part of the pathogenesis study of V. vulnificus septicemia. Bactericidal activity of serum against V. vulnificus was complement-dependent and the alternative pathway played the major role. V. vulnificus strains CDC A1402 and ATCC 27562 appeared serum-sensitive, and CDC C7184, clinical isolate CNUH1 and ATCC 29307 were serum-resistant. When bactericidal activity of cirrhotic sera against serum-sensitive CDC A1402 and serum-resistant CDC C7184 was compared with that of normal sera. showed slightly poorer bactericidal activity than normal sera. Especially in the case of serum-resistant CDC C7184 strain, cirrhotic sera showed statistically significant decrease(p<0.05) in their bactericidal activity.

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On the Coastline Date Compression in Digital Chart Selecting Conspicuous Coast Positiona as Node Points (현저한 해안 위치를 절점으로 선정하는 디지털 해도에서의 해안선 데이터 압축)

  • 임정빈;고광섭;최낙현
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.4 no.1
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    • pp.13-20
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    • 1998
  • Since the digital chart consists of a large number of points, the effective method for the coastline data compression(CDC), storing the data compactly and reproducting the coastline feature accurately, is important. In the CDC, the key technique is to determine the optimal positions as node points in given coastlines. In this paper, a new CDC method, selecting node points with conspicuous coast positions in the view point on navigation and adopting spline interpolation to the nodes partly, is proposed. Using the northern part of KEOJE-DO coastline in Korean chart No.204, CDC experiments are carrie out with various compression ratio. The results fro the influence of coastline shape according to various CDC methods are discussed and presented.

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