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Interacting network of Hippo, Wnt/β-catenin and Notch signaling represses liver tumor formation
( Wantae Kim ),( Sanjoy Kumar Khan ),( Yingzi Yang ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.1
Acquiring a selective growth advantage by breaking the proliferation barrier established by gatekeeper genes is a centrally important event in tumor formation. Removal of the mammalian Hippo kinase Mst1 and Mst2 in hepatocytes leads to rapid hepatocellular carcinoma (HCC) formation, indicating that the Hippo signaling pathway is a critical gatekeeper that restrains abnormal growth in hepatocytes. By rigorous genetic approaches, we identified an interacting network of the Hippo, Wnt/β-catenin and Notch signaling pathways that control organ size and HCC development. We found that in hepatocytes, the loss of Mst1/2 leads to the activation of Notch signaling, which forms a positive feedback loop with Yap/Taz (transcription factors controlled by Mst1/2). This positive feedback loop results in severe liver enlargement and rapid HCC formation. Blocking the Yap/Taz-Notch positive feedback loop by Notch inhibition in vivo significantly reduced the Yap/Taz activities, hepatocyte proliferation and tumor formation. Furthermore, we uncovered a surprising inhibitory role of Wnt/β-catenin signaling to Yap/Taz activities, which are important in tumor initiation. Genetic removal of β-catenin in the liver of the Mst1/2 mutants significantly accelerates tumoriogenesis. Therefore, Wnt/β-catenin signaling, known for its oncogenic property, exerts an unexpected function in restricting Yap/Taz and Notch activities in HCC initiation. The molecular interplay between the three signaling pathways identified in our study provides new insights in developing novel therapeutic strategies to treat liver tumors. [BMB Reports 2017; 50(1): 1-2]
The history and regulatory mechanism of the Hippo pathway
( Wantae Kim ),( Eek-hoon Jho ) 생화학분자생물학회(구 한국생화학분자생물학회) 2018 BMB Reports Vol.51 No.3
How the organ size is adjusted to the proper size during development and how organs know that they reach the original size during regeneration remain long-standing questions. Based on studies using multiple model organisms and approaches for over 20 years, a consensus has been established that the Hippo pathway plays crucial roles in controlling organ size and maintaining tissue homeostasis. Given the significance of these processes, the dysregulation of the Hippo pathway has also implicated various diseases, such as tissue degeneration and cancer. By regulating the downstream transcriptional coactivators YAP and TAZ, the Hippo pathway coordinates cell proliferation and apoptosis in response to a variety of signals including cell contact inhibition, polarity, mechanical sensation and soluble factors. Since the core components and their functions of the Hippo pathway are evolutionarily conserved, this pathway serves as a global regulator of organ size control. Therefore, further investigation of the regulatory mechanisms will provide physiological insights to better understand tissue homeostasis. In this review, the historical developments and current understandings of the regulatory mechanism of Hippo signaling pathway are discussed. [BMB Reports 2018; 51(3): 106-118]
Kim, Wantae,Chung, Dae-won,Kim, Jeong Ho Wiley Subscription Services, Inc., A Wiley Company 2008 Journal of applied polymer science Vol.110 No.5
<P>Polyether- and polyester-based thermoplastic polyurethane (TPU) nanocomposites containing the montmorillonite modified with quaternary ammonium salts having a relatively long hydroxyalkyl branch (MMT-OH) were prepared via solution mixing. Quaternary ammonium salts with dimethyl, octyl, hydroxyundecyl branches were synthesized by the addition reaction of dimethyloctylamine and 11-bromo-1-undecanol and were used for the preparation of MMT-OH. In this MMT-OH clay, hydroxyl groups are located at the outer end of the relatively long undecyl branch, which may make the hydroxyl groups more exposed to the matrix polymers compared to the clays with the modifiers having shorter hydroxyalkyl chain such as C30B. Actually, more hydroxyl groups in MMT-OH's are thought to be exposed outside the modified clay, since MMT-OH's were observed to be somewhat dispersed in water, while clays with shorter alkyl chains were not. From XRD and TEM results, the silicate layers of MMT-OH were shown to be very well dispersed in ether-TPU and ester-TPU nanocomposites prepared from dimethyl acetamide solution. In the case of ester-TPU nanocomposites, much better clay dispersion was observed for nanocomposites containing MMT-OH than the ones with C30B in the TEM images. The tensile properties measurement showed the similar trend. Although MMT-OH has only one hydroxyl group while C30B has two, above results of better tensile properties and water dispersibility of MMT-OH than C30B having two hydroxyls indicate that the position of hydroxyls may be a important factor in determining the properties of TPU/clay nanocomposites. Fourier transform infrared spectroscopy analyses showed that the long hydroxyalkyl chain modifiers may provide more hydrogen bonding sites than short hydroxyalkyl chain modifiers. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008</P>
Wnt/β-catenin signalling: from plasma membrane to nucleus.
Kim, Wantae,Kim, Minseong,Jho, Eek-hoon Biochemical Society 2013 Biochemical journal Vol.450 No.1
<P>Wnt/β-catenin signalling plays essential roles in embryonic development as well as tissue homoeostasis in adults. Thus abnormal regulation of Wnt/β-catenin signalling is linked to a variety of human diseases, including cancer, osteoporosis and Alzheimer's disease. Owing to the importance of Wnt signalling in a wide range of biological fields, a better understanding of its precise mechanisms could provide fundamental insights for therapeutic applications. Although many studies have investigated the regulation of Wnt/β-catenin signalling, our knowledge remains insufficient due to the complexity and diversity of Wnt signalling. It is generally accepted that the identification of novel regulators and their functions is a prerequisite to fully elucidating the regulation of Wnt/β-catenin signalling. Recently, several novel modulators of Wnt signalling have been determined through multiple genetic and proteomic approaches. In the present review, we discuss the mechanistic regulation of Wnt/β-catenin signalling by focusing on the roles of these novel regulators.</P>
Sonochemical Synthesis of Zeolite A from Metakaolinite in NaOH Solution
Kim, Wantae,Choi, Doyoung,Kim, Sangbae The Japan Institute of Metals 2010 MATERIALS TRANSACTIONS Vol.51 No.9
<P>Sonochemical synthesis of zeolite A has been conducted by ultrasonic irradiation of mixtures of metakaolinite and NaOH solution. The hydrothermal synthesis at conventional synthesis conditions was undertaken to determine the sonochemical reliability. The enhancement of nucleation and crystallization rate of zeolite A was achieved by ultrasound. In the ultrasonic field, zeolite A once formed in the suspension has been converted into hydroxysodalite and losod as sonicating proceeded. Comparing the results with those of conventional methods, this heterogeneous reaction was particularly accelerated by ultrasound, leading to improved reactivity of solid reactant through intensive mixing. The use of ultrasound enables us to prepare well-dispersed fine zeolite A particles with mean particle size of around 1 μm. The cation exchange capacity values of the products increased as the synthesis reaction for zeolite A proceeded. The high solid concentration in the suspension, however, hindered the ultrasound from intense agitating, resulting in the decrease of zeolite A yield.</P>
김완태(WanTae Kim),이경민(KyoungMin Lee),김진년(JinNyun Kim),차영욱(YoungWook Cha) 한국정보기술학회 2011 Proceedings of KIIT Conference Vol.2011 No.5
기존 인터넷의 경직화 문제를 위한 장기적인 해결책으로 가상화 기술이 각광받고 있다. 많은 기관에서 가상화 기반의 미래 인터넷 테스트-베드와 연구 프로젝트들을 진행하고 있다. 본 논문에서는 ICT(Information and Communications Technology) 환경에서의 통합 자원을 관리하는 미래 인터넷의 가상화 플랫폼을 구축하였으며, 실험-중심 연구를 위하여 가상네트워크와 가상서버로 구성되는 슬라이스 생성의 실현성을 확인하였다. Network virtualization has been concerned as long term solution for ossification problem of Internet. Many organizations have been carrying out test-bed and research projects of future Internet based on virtualization. In this paper, we built up virtualization platform managing integrated resources in ICT environment and checked out the feasibility of slice consisting of virtual network and virtual server for experiment-centric research.