• Title/Summary/Keyword: CUG2

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Cancer-Upregulated Gene 2 (CUG2), a New Component of Centromere Complex, Is Required for Kinetochore Function

  • Kim, Hyejin;Lee, Miae;Lee, Sunhee;Park, Byoungwoo;Koh, Wansoo;Lee, Dong Jun;Lim, Dae-Sik;Lee, Soojin
    • Molecules and Cells
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    • v.27 no.6
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    • pp.697-701
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    • 2009
  • We previously identified cancer-upregulated gene 2 (CUG2) as a commonly up-regulated gene in various human cancer tissues, especially in ovary, liver, and lung (Lee et al., 2007a). CUG2 was determined to be a nuclear protein that exhibited high proto-oncogenic activities when overexpressed in NIH3T3 mouse fibroblast cells. To identify other cellular functions of CUG2, we performed yeast two-hybrid screening and identified CENP-T, a component of CENP-A nucleosome complex in the centromere, as an interacting partner of CUG2. Moreover, CENP-A, the principle centromeric determinant, was also found in complex with CENP-T/CUG2. Immunofluorescent staining revealed the co-localization of CUG2 with human centromeric markers. Inhibition of CUG2 expression drastically affected cell viability by inducing aberrant cell division. We propose that CUG2 is a new component of the human centromeric complex that is required for proper chromosome segregation during mitosis.

Effective User Clustering Algorithm for Collaborative Filtering System (협력적 여과 시스템을 위한 효과적인 사용자 군집 알고리즘)

  • Go, Su-Jeong;Im, Gi-Uk;Lee, Jeong-Hyeon
    • The KIPS Transactions:PartB
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    • v.8B no.2
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    • pp.144-154
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    • 2001
  • 협력적 여과 시스템은 사용자가 검색하고 읽었던 웹문서를 기반으로 사용자 군집을 생성하여 웹문서의 정확한 추천을 가능하게 한다. 이러한 목적으로 설계된 다양한 알고리즘이 있으나 속도가 느리거나 정확도가 낮다는 등의 단점이 있다. 본 논문에서는 이러한 단점을 보완하기 위하여 협력적 여과 시스템을 위한 효과적인 사용자 군집 알고리즘인 CUG알고리즘은 사용자 군집을 생성하기 위해 Apriori 알고리즘, Native Bayes 알고리즘을 이용한다. Apriori 알고리즘은 연관 단어 지식 베이스를 구축하고, Native Bayes 알고리즘은 구축된 연관 단어 지식 베이스에 가중치를 추가하며, 사용자가 검색하여 읽은 웹문서를 클래스별로 분류한다. CUG 알고리즘은 분류된 웹문서를 기반으로 하여 사용자 군집을 만든다. 이러한 방법으로 설계된 CUG 알고리즘은 사용자들이 사용할 문서를 미리 검색하여 저장함에 의해 정보검색의 효율성을 향상시키는데 사용될 수 있다. 본 논문에서 설계한 CUG 알고리즘의 선능을 평가하기 위하여 기존의 K-means 방법과 Gibbs샘플링 방법에 의한 군집과 비교한다.

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The Decreased Expression of Fbxw7 E3 Ligase Mediated by Cancer Upregulated Gene 2 Confers Cancer Stem Cell-like Phenotypes (CUG2 유전자에 의하여 감소된 FBXW7 E3 ligase 발현이 유사-종양줄기세포 표현형을 유도)

  • Yawut, Natpaphan;Kim, Namuk;Budluang, Phatcharaporn;Cho, Il-Rae;Kaowinn, Sirichat;Koh, Sang Seok;Kang, Ho Young;Chung, Young-Hwa
    • Journal of Life Science
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    • v.32 no.4
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    • pp.271-278
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    • 2022
  • The detailed mechanism by which cancer upregulated gene 2 (CUG2) overexpression induces cancer stem cell-like phenotypes is not fully understood. The downregulation of FBXW7 E3 ligase, a tumor suppressor known for its proteolytic regulation of oncogenic proteins such as cyclin E, c-Myc, Notch, and Yap1, has been frequently reported in several types of tumor tissues, including those in the large intestine, cervix, and stomach. Therefore, we investigated whether FBXW7 is involved in CUG2-induced oncogenesis. In this study, the decreased expression of FBXW7 was examined in human lung adenocarcinoma A549 (A549-CUG2) and human bronchial BEAS-2B cells (BEAS-CUG2) overexpressing CUG2 and compared with control cells stably expressing an empty vector (A549-Vec or BEAS-Vec). Treatment with MG132 (a proteosome inhibitor) prevented the degradation of FBXW7 and Yap1 proteins, which are substrates of the FBXW7 E3 ligase. To address the role of Fbxw7 in the development of cancer stem cell (CSC) phenotypes, we suppressed Fbxw7 protein levels using its siRNA. We observed that decreased levels of FBXW7 enhanced cell migration, invasion, and spheroid size and number in A549-Vec and BEAS-Vec cells. The enforced expression of FBXW7 produced the opposite results in A549-CUG2 and BEAS-CUG2 cells. Furthermore, the downregulation of FBXW7 elevated the activities of EGFR, Akt, and ERK1/2 and upregulated β-catenin, Yap1, and NEK2, while the enforced expression of FBXW7 generated the opposite results. We thus propose that FBXW7 downregulation induced by CUG2 confers CSC-like phenotypes through the upregulation of both the EGFR-ERK1/2 and β-catenin-Yap1-NEK2 signaling pathways.

Implementation of Telecomunication Networks by means of Closed User Group :A Case Study of Kuk-Jae Construction Company (CUG에 의한 원거리정보통신망 구축과 활용: 국제종합건설 사례)

  • 이국희;송수섭
    • The Journal of Information Technology and Database
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    • v.1 no.2
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    • pp.147-157
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    • 1994
  • CUG(Closed User Group)란 하이텔, 천리안, 포스서브망에서 특정기업의 이용자만이 접속할 수 있도록 마련된 독립적인 통신망 서비스이다. 이 글에서는 이러한 CUG 서비스를 이용하여 전국 각지의 40여개 현장과의 원거리통신망을 성공적으로 운영하고 있는 국제종합건설사례를 분석한다. 주로 문서수발 비용과 시간을 줄이고, 정보분실을 피하기 위해서 도입되었던 CUG는 3년간에 걸친 운영 결과 여러가지 분야에서 업무개선과 바람직한 방향으로의 질적변화를 발생하였다. CUG는 저렴한 비용, 확장용이성, 안정성으로 인해 느슨하게 연결된(loosely coupled) 조직 사이의 원거리통신망 구축에 유력한 대안으로 판단되나, 그 자체가 일반 PC통신망이 가지고 있는 취약한 기능성, 성능, 보안 문제로 인해 본질적인 한계를 가지고 있었다. 사례를 통해 한 기업의 구조, 업무절차, 문화에 적합한 통신수단이 무엇이며, 그것을 어떻게 활용하느냐라는 관점의 중요성이 강조되고 있다.

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Translocalization of enhanced PKM2 protein into the nucleus induced by cancer upregulated gene 2 confers cancer stem cell-like phenotypes

  • Yawut, Natpaphan;Kaowinn, Sirichat;Cho, Il-Rae;Budluang, Phatcharaporn;Kim, Seonghye;Kim, Suhkmann;Youn, So Eun;Koh, Sang Seok;Chung, Young-Hwa
    • BMB Reports
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    • v.55 no.2
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    • pp.98-103
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    • 2022
  • Increased mRNA levels of cancer upregulated gene (CUG)2 have been detected in many different tumor tissues using Affymetrix microarray. Oncogenic capability of the CUG2 gene has been further reported. However, the mechanism by which CUG2 overexpression promotes cancer stem cell (CSC)-like phenotypes remains unknown. With recent studies showing that pyruvate kinase muscle 2 (PKM2) is overexpressed in clinical tissues from gastric, lung, and cervical cancer patients, we hypothesized that PKM2 might play an important role in CSC-like phenotypes caused by CUG2 overexpression. The present study revealed that PKM2 protein levels and translocation of PKM2 into the nucleus were enhanced in CUG2-overexpressing lung carcinoma A549 and immortalized bronchial BEAS-2B cells than in control cells. Expression levels of c-Myc, CyclinD1, and PKM2 were increased in CUG2-overexpressing cells than in control cells. Furthermore, EGFR and ERK inhibitors as well as suppression of Yap1 and NEK2 expression reduced PKM2 protein levels. Interestingly, knockdown of β-catenin expression failed to reduce PKM2 protein levels. Furthermore, reduction of PKM2 expression with its siRNA hindered CSC-like phenotypes such as faster wound healing, aggressive transwell migration, and increased size/number of sphere formation. The introduction of mutant S37A PKM2-green fluorescence protein (GFP) into cells without ability to move to the nucleus did not confer CSC-like phenotypes, whereas forced expression of wild-type PKM2 promoted such phenotypes. Overall, CUG2-induced increase in the expression of nuclear PKM2 contributes to CSC-like phenotypes by upregulating c-Myc and CyclinD1 as a co-activator.

Mechanisms of Myotonic Dystrophies 1 and 2

  • Lubov, Timchenko
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.1
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    • pp.1-8
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    • 2005
  • Myotonic Dystrophies type 1 and 2 (DM1/2) are neuromuscular disorders which belong to a group of genetic diseases caused by unstable CTG triplet repeat (DM1) and CCTG tetranucleotide repeat (DM2) expansions. In DM1, CTG repeats are located within the 3' untranslated region of myotonin protein kinase (DMPK) gene on chromosome 19q. DM2 is caused by expansion of CCTG repeats located in the first intron of a gene coding for zinc finger factor 9 on chromosome 3q. The CTG and CCTG expansions are located in untranslated regions and are expressed as pre-mRNAs in nuclei (DM1 and DM2) and as mRNA in cytoplasm (DM1). Investigations of molecular alterations in DM1 discovered a new molecular mechanism responsible for this disease. Expansion of un-translated CUG repeats in the mutant DMPK mRNA disrupts biological functions of two CUG-binding proteins, CUGBP and MNBL. These proteins regulate translation and splicing of mRNAs coding for proteins which play a key role in skeletal muscle function. Expansion of CUG repeats alters these two stages of RNA metabolism in DM1 by titrating CUGBP1 and MNBL into mutant DMPK mRNA-protein complexes. Mouse models, in which levels of CUGBP1 and MNBL were modulated to mimic DM1, showed several symptoms of DM1 disease including muscular dystrophy, cataracts and myotonia. Mis-regulated levels of CUGBP1 in newborn mice cause a delay of muscle development mimicking muscle symptoms of congenital form of DM1 disease. Since expansion of CCTG repeats in DM2 is also located in untranslated region, it is predicted that DM2 mechanisms might be similar to those observed in DM1. However, differences in clinical phenotypes of DM1 and DM2 suggest some specific features in molecular pathways in both diseases. Recent publications suggest that number of pathways affected by RNA CUG and CCUG repeats could be larger than initially thought. Detailed studies of these pathways will help in developing therapy for patients affected with DM1 and DM2.

Construction and characterization of heterozygous diploid Escherichia coli (2배체 대장균의 제조와 그 특성)

  • Jung, Hyeim;Lim, Dongbin
    • Korean Journal of Microbiology
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    • v.52 no.4
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    • pp.406-414
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    • 2016
  • Among 6 leu codons, CUG is the most frequently used codon in E. coli. It is recognized by leu-tRNA(CAG) encoded by four genes scattered on two chromosomal loci (leuT and leuPQV ). In the process of constructing a strain with no functional leu-tRNA (CAG) gene on chromosome, we made two mutant strains separately, one on leuPQV locus (${\Delta}leuPQV$), and the other on leuT locus [$leuT^*$(GAG)], where the anticodon of leuT was changed from CAG to GAG, thereby altering its recognition codon from CUG to CUC. We attempted to combine these two mutations by transduction using $leuT^*$(GAG) strain as a donor and ${\Delta}leuPQV$ strain as a recipient. Large and small colonies appeared from this transduction. From PCR and DNA sequencing, large colony was confirmed to be the reciprocal recombinant as expected, but the small colonies contained both mutant $leuT^*$(GAG) and wild type leuT (CAG) genes in the cell. This heterozygous diploid strain did not show any unusual morphology under microscopic observation, but, interestingly, it showed a linear growth curve in rich medium with much slower growth rate than wild type cell. It always formed homogenous small colonies in the selection medium, but, when there was no selection, it readily segregated into $leuT^*$(GAG) and leuT (CAG). From these observations, we suggested that the strain with both $leuT^*$(GAG) and leuT (CAG) genes was not a partial diploid (merodiploid), but a full diploid cell having two different chromosomes. We proposed a model explaining how such a heterozygous diploid cell was formed and how and why its growth showed a linear growth curve.

Design and Implementation of a Peer-to-Peer Data Sharing Scheme for Closed User Group with Security and Flexibility (보안성과 유연성을 갖춘 Peer-to-Peer 데이터 공유 기법의 설계 및 구현)

  • Lee Goo-Yeon;Lee Yong;Kim Hwa-Jong;Jeong Choong-Kyo;Lee Dong-Eun
    • Journal of the Korea Institute of Information Security & Cryptology
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    • v.15 no.4
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    • pp.61-70
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    • 2005
  • We propose and implement a flexible secure peer-to-peer(P2P) file sharing scheme which can be used for data sharing among closed user group (CUG) members. When a member wants to share data, notification messages are sent to the members with whom the member wants to share data. Each notification message includes one-time password encrypted with the receiver's public key. A member who received the notification message can download the data by using the one-time password. The proposed scheme provides selective sharing, download confirmation and efficient storage management. In terms of security, the proposed scheme supports authentication, entity privacy, replay attack protection and disguise prevention. We also implement the proposed system and find that the system is very useful among P2P service of closed user groups.

A Homeotic Gene, Hoxc8, Regulates the Expression of Proliferating Cell Nuclear Antigen in NIH3T3 Cell

  • Min, Hye-Hyun;Kang, Myeng-Mo;Kim, Myoung-Hee
    • Biomedical Science Letters
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    • v.13 no.3
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    • pp.239-244
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    • 2007
  • Hoxc8 is one of the homeotic developmental control genes regulating the expression of many downstream target genes, through which animal body pattern is established during embryonic development. In previous proteomics analysis, proliferating cell nuclear antigen (PCNA) which is also known as cyclin, has been implied to be regulated by Hoxc8 in F9 murine embryonic teratocarcinoma cell. When the 5' upstream region of PCNA was analyzed, it turned out to contain 20 Hox core binding sites (ATTA) in about 1.17 kbp (kilo base pairs) region ($-520{\sim}-1690$). In order to test whether this region is responsible for Hoxc8 regulation, the upstream 2.3 kbp fragment of PCNA was amplified through PCR and then cloned into the pGL3 basic vector containing a luciferase gene as a reporter. When the luciferase activity was measured in the presence of effector plasmid (pcDNA : c8) expressing murine Hoxc8, the PCNA promoter driven reporter activity was reduced. To confirm whether this reduction is due to the Hoxc8 protein, the siRNA against Hoxc8 (5'-GUA UCA GAC CUU GGA ACU A-3' and 5'-UAG UUC CAA GGU CUG AUA C-3') was prepared. Interestingly enough, siRNA treatment up regulated the luciferase activity which was down regulated by Hoxc8, indicating that Hoxc8 indeed regulates the expression of PCNA, in particular, down regulation in NIN3T3 cells. These results altogether indicate that Hoxc8 might orchestrate the pattern formation by regulating PCNA which is one of the important proteins involved in several processes such as DNA replication and methylation, chromatin remodeling, cell cycle regulation, differentiation, as well as programmed cell death.

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