• 제목/요약/키워드: Binding Mechanism

검색결과 993건 처리시간 0.029초

Survival of APC-mutant colorectal cancer cells requires interaction between tankyrase and a thiol peroxidase, peroxiredoxin II

  • Kang, Dong Hoon;Lee, Joanna H.S.;Kang, Sang Won
    • BMB Reports
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    • 제50권8호
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    • pp.391-392
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    • 2017
  • Overexpression of mammalian 2-Cys peroxiredoxin (Prx) enzymes is observed in most cancer tissues. Nevertheless, their specific roles in colorectal cancer (CRC) progression has yet to be fully elucidated. Here, a novel molecular mechanism by which PrxII/Tankyrase (TNKS) interaction mediates survival of adenomatous polyposis coli (APC)-mutant CRC cells was explored. In mice with an inactivating APC mutation, a model of spontaneous intestinal tumorigenesis, deletion of PrxII reduced intestinal adenomatous polyposis and thereby increased survival. In APC-mutant human CRC cells, PrxII depletion hindered PARP-dependent Axin1 degradation through TNKS inactivation. $H_2O_2-sensitive$ Cys residues in the zinc-binding domain of TNKS1 was found to be crucial for PARsylation activity. Mechanistically, direct binding of PrxII to ARC4/5 domains of TNKS conferred vital redox protection against oxidative inactivation. As a proof-of-concept experiment, a chemical compound targeting PrxII inhibited the growth of tumors xenografted with APC-mutation-positive CRC cells. Collectively, the results provide evidence revealing a novel redox mechanism for regulating TNKS activity such that physical interaction between PrxII and TNKS promoted survival of APC-mutant colorectal cancer cells by PrxII-dependent antioxidant shielding.

Modulation of autophagy by miRNAs

  • Kim, Yunha;Lee, Junghee;Ryu, Hoon
    • BMB Reports
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    • 제48권7호
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    • pp.371-372
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    • 2015
  • MicroRNAs (miRNAs) can regulate the expression of genes that are involved in multiple cellular pathways. However, their targets and mechanism of action associated with the autophagy pathway are not fully investigated yet. EWSR1 (EWS RNA-Binding Protein 1/Ewing Sarcoma Break Point Region 1) gene encodes a RNA/DNA binding protein that is ubiquitously expressed and plays roles in numerous cellular processes. Recently, our group has shown that EWSR1 deficiency leads to developmental failure and accelerated senescence via processing of miRNAs, but its role in the regulation of autophagy remains elusive. In this context, we further investigated and found that EWSR1 deficiency triggers the activation of the DROSHA-mediated microprocessor complex and increases the levels of miR125a and miR351, which directly target Uvrag. Interestingly, the miR125a- and miR351-targeted reduction of Uvrag led to the inhibition of autophagy in both ewsr1 knockout (KO) MEFs and ewsr1 KO mice. In summary, our study demonstrates that EWSR1 is associated with the posttranscriptional regulation of Uvrag via miRNA processing. The regulation of autophagy pathway in miRNAs-Uvrag-dependent manner provides a novel mechanism of EWSR1 deficiency-related cellular dysfunction. [BMB Reports 2015; 48(7): 371-372]

Mechanism of Apatite Formation on Bioactive Titanium Metal

  • Kim, Hyun-Min;Takadama, Hiroaki;Miyaji, Fumiaki;Kokubo, Tadashi;Nishiguchi, Shigeru;Nakamura, Takashi
    • The Korean Journal of Ceramics
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    • 제4권4호
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    • pp.336-339
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    • 1998
  • Bioactive titanium metal can be prepared by simple 5M-NaOH treatment and subsuquent heat treatment at $600^{\circ}C$ to form an amorphous sodium titanate on its surface. In the present study, mechanism of apatite formation on the titanium metal was investigated by examining its surface compositional and structural changes in a simulated body fluid. The apatite formation on the metal was found to proceed in the sequence of 1)$Na^+$ ion release from the sodium titanate to form hydrated titania abundant in Ti-OH groups, 2) early and selective binding of calcium ions with the Ti-OH groups to form a calcium titanate, and 3) late binding of phosphate ions to make apatite nucleation and growth. This indicates that Ti-OH groups do not directly induce the apatite nucleation, but via formation of a calcium titanate.

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LDB2 regulates the expression of DLL4 through the formation of oligomeric complexes in endothelial cells

  • Choi, Hyun-Jung;Rho, Seung-Sik;Choi, Dong-Hoon;Kwon, Young-Guen
    • BMB Reports
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    • 제51권1호
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    • pp.21-26
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    • 2018
  • Delta-like ligand 4 (DLL4) expression in endothelial cells is intimately associated with angiogenic sprouting and vascular remodeling, but the precise mechanism of transcriptional regulation of DLL4 remains incompletely understood. Here, we showed that LIM-domain binding protein 2 (LDB2) plays an important role in regulating basal DLL4 and VEGF-induced DLL4 expression. Knockdown of LDB2 using siRNA enhanced endothelial sprouting and tubular network formation in vitro. Injection of ldb2-morpholino resulted in defective development of intersegmental vessels in zebrafish. Reduction or over-expression of LDB2 in endothelial cells decreased or increased DLL4 expression. LDB2 regulated DLL4 promoter activity by binding to its promoter region and the same promoter region was occupied and regulated by the LMO2/TAL1/GATA2 complex. Interestingly, LDB2 also mediated VEGF-induced DLL4 expression in endothelial cells. The regulation of DLL4 by the LDB2 complex provides a novel mechanism of DLL4 transcriptional control that may be exploited to develop therapeutics for aberrant vascular remodeling.

일반화된 계층적 MIPv6 환경에서의 안전한 바인딩 업데이트 및 Fast Handover를 위한 인증 메커니즘 (Authentication Mechanism for Secure Binding Update and Fast Handover in the Generalized Hierarchical MIPv6)

  • 박창섭;강현선
    • 정보보호학회논문지
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    • 제18권2호
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    • pp.107-115
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    • 2008
  • 본 논문에서는 일반화된 계층적 MIPv6 환경에서의 안전하고 효율적인 바인딩 업데이트 및 핸드오버 프로토콜을 제안한다. 기존의 계층적 MIPv6 환경에서의 바인딩 업데이트는 보편적으로 foreign network가 소규모 MAP 도메인으로 구성된다. 하지만, 제안 프로토콜에서는 다수의 MAP들이 계층적으로 구성되어지는 대규모 네트워크 환경에서의 안전하고 신속한 이동성 지원을 위한 메커니즘을 소개한다. 또한 다양한 공격 시나리오를 통해 제안 메커니즘의 안전성을 분석한다.

HoAaRO: Home Agent-Assisted Route Optimization Protocol for Nested Network

  • Sun, Shi-Min;Lee, Sang-Min;Nam, Ki-Ho;Kim, Jong-Wan;Yoo, Jae-Pil;Kim, Kee-Cheon
    • 한국정보처리학회:학술대회논문집
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    • 한국정보처리학회 2008년도 춘계학술발표대회
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    • pp.1035-1038
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    • 2008
  • Network mobility (NEMO) has been studied extensively due to its potential applications in military and public transportation. NEMO Basic Support Protocol (NBSP) [1], the current NEMO standard based on mobile IPv6, can be readily deployed using the existing mobile IPv6 infrastructure. However, for Nested network mobility, multi-level tunnel and too many Binding Update packets results in substantial performance overhead, generally known as route sub-optimality, especially in the bottleneck root mobile router (root-MR) and Access Router. In this paper, we propose a route optimization mechanism for nested network mobility management to reduce the overhead of root-MR. In this system, Mobile Router (MR) has a cache that stores Mobile Network Nodes' (MNN) information, Correspondent Nodes' (CN) information for every MNN,and the attachments information with its subnet MRs. Home Agent performs Binding Update with CNs responsible for MRs. Through this mechanism, the number of tunnel is limited between CN and MR and the overhead of root-MR is reduced obviously.

Theoretical Investigations on Structure and Function of Human Homologue hABH4 of E.coli ALKB4

  • Shankaracharya, Shankaracharya;Das, Saibal;Prasad, Dinesh;Vidyarthi, Ambarish Sharan
    • Interdisciplinary Bio Central
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    • 제2권3호
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    • pp.8.1-8.5
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    • 2010
  • Introduction: Recently identified human homologues of ALKB protein have shown the activity of DNA damaging drugs, used for cancer therapy. Bioinformatics study of hABH2 and hABH3 had led to the discovery of a novel DNA repair mechanism. Very little is known about structure and function of hABH4, one of the members of this superfamily. Therefore, in present study we are intended to predict its structure and function through various bioinformatics tools. Materials and Methods: Modeling was done with modeler 9v7 to predict the 3D structure of the hABH4 protein. This model was validated with the program Procheck using Ramachandran plot statistics and was submitted to PMDB with ID PM0076284. The 3d2GO server was used to predict the functions. Residues at protein ligand and protein RNA binding sites were predicted with 3dLigandSite and KYG programs respectively. Results and Discussion: 3-D model of hABH4, ALKBH4.B99990003.pdb was predicted and evaluated. Validation result showed that 96.4 % residues lies in favored and additional allowed region of Ramachandran plot. Ligand binding residues prediction showed four Ligand clusters, having 24 ligands in cluster 1. Importantly, conserved pattern of Glu196-X-Pro198- Xn-His254 in the functional domain was detected. DNA and RNA binding sites were also predicted in the model. Conclusion and Prospects: The predicted and validated model of human homologue hABH4 resulted from this study may unveil the mechanism of DNA damage repair in human and accelerate the research on designing of appropriate inhibitors aiding in chemotherapy and cancer related diseases.

화학적으로 변형된 하수슬러지를 이용한 반응성염료의 생물흡착 (Biosorption of Reactive Dyes using Chemically Modified Sewage Sludge)

  • 한민희;최기욱;윤영상
    • 청정기술
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    • 제13권3호
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    • pp.215-221
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    • 2007
  • 생물흡착은 염색폐수로부터 염료를 제거하기 위한 기술로서 현재 사용되고 있는 기술을 대체할 수 있는 유망한 처리 방법이다. 본 연구에서는 생물흡착제로써 저가이면서 풍부한 소재중의 하나인 하수 슬러지를 이용하였다. 본 연구의 목적은 바이오매스의 변형을 통하여 흡착능력을 향상시키는데 있다. FT-IR 분석과 적정실험을 통하여 흡착에 관여하는 작용기는 카르복실 그룹, 인산 그룹, 아민 그룹으로 판명하였으며 그 중에서 반응성 염료(Reactive Red 4, RR 4)를 흡착할 수 있는 작용기는 아민 그룹임을 알 수 있었다. 또한 음이온성 염료인 RR 4의 흡착을 저해하는 것으로 생각되는 카르복실 그룹을 제거함으로써 흡착성능을 향상시킬 수 있었다. 그 결과, 카르복실 그룹이 제거된 바이오매스의 최대 흡착량이 변형 전에 비해 pH 2에서는 130%, pH 4에서는 210% 증가하였다. 그러므로 화학적으로 변형시킨 하수 슬러지는 산업폐수내 염료제거에 효과적이면서 값싼 생물흡착제로 이용될 수 있을 것으로 기대된다.

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Ginsenoside Rb2 Upregulates the Low Density Lipoprotein Receptor Gene Expression through the Activation of the Sterol Regulated Element Binding Protein Maturation in HepG2 Cells

  • Lim, Grewo;Lee, Hyunil;Kim, Eun-Ju;Noh, Yun-Hee;Ro, Youngtae;Koo, Ja-Hyun
    • Journal of Ginseng Research
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    • 제29권4호
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    • pp.159-166
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    • 2005
  • Ginsenosides, a group of Panax ginseng saponins, exert the lowering effects of plasma cholesterol levels in animals. We had reported earlier that ginsenoside Rb2 upregulate low-density lipoprotein receptor (LDLR) expression via a mechanism that is dependent of the activation of sterol response element binding protein 2 (SREBP-2) expression. This study was conducted to determine the effects of ginsenoside Rb2 on the expression of the hepatic LDLR expression at cellular levels using HepG2 cells, and to evaluate whether the sterol response element binding protein 1 (SREBP-l) was involved in the regulation of LDLR expression. Incubation of HepG2 cells in serum-free medium supplemented with cholesterol $(10{\mu}g/ml)$ for 8 hours decreased the mRNAs of LDLR mRNA by $12\%$ and SREBP-l mRNA by $35\%$. Ginsenoside Rb2 antagonized the repressive effects of cholesterol and increased both LDLR and SREBP-l mRNA expression to 1.5- and 2-fold, respectively. Furthermore, Western blot and confocal microscopic analyses with SREBP-l polyclonal antibody revealed that ginsenoside Rb2 enhanced the maturation of the SREBP-1 from the inactive precursor form in ER membrane to the active transcription factor form in nucleus. These results suggest that ginsenoside Rb2 upregulates LDLR expression via a mechanism that is dependent of the activation of not only SREBP-2 expression, but also SREBP-1 expression and maturation, and also indicate that the pharmacological value of ginsenoside Rb2 may be distinguished from that of lovastatin which is reported that it upregulate LDLR through SREBP-2 only, not through SREBP-1.

온라인 간편결제 서비스 사용 활성화에 대한 연구 (A Study on the Facilitating Usage of Online Simple Payment Service)

  • 연다인;문동지;김희웅
    • 한국정보시스템학회지:정보시스템연구
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    • 제27권4호
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    • pp.203-227
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    • 2018
  • Purpose The purpose of this study is to investigate which decision factors continue to use the service based on the online simple payment service. In this study, we will examine how to activate the service from the continuing factors through the dual-model theory consisting of personal dedication and constraint dedication which are frequently used in relation marketing. Design/methodology/approach In this study, we investigated the activation of online simple settlement service using factors affecting the preference of the simple payment service based on the dual-model of dedication-based mechanism and constraint-based mechanism. Findings This study confirmed that customer satisfaction and convenience under the dedication -based mechanism were found to be linked to the preference of the simple payment service. Switching cost under the constraint - based mechanism showed that the customer had no binding ability to continue using the service of the current provider. Likewise, preference was found to have a direct effect on the actual frequency of use of the simple payment service, the number of uses compared to the total number of online payments, and willingness to use more.