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Obtusilactone B from Machilus Thunbergii targets barrier-to-autointegration factor to treat cancer.
Kim, Wanil,Lyu, Ha-Na,Kwon, Hyun-Sook,Kim, Ye Seul,Lee, Kyung-Ha,Kim, Do-Yeon,Chakraborty, Goutam,Choi, Kwan Yong,Yoon, Ho Sup,Kim, Kyong-Tai American Society for Pharmacology and Experimental 2013 Molecular pharmacology Vol.83 No.2
<P>Targeting specific molecules is a promising cancer treatment because certain types of cancer cells are dependent on specific oncogenes. This strategy led to the development of therapeutics that use monoclonal antibodies or small-molecule inhibitors. However, the continued development of novel molecular targeting inhibitors is required to target the various oncogenes associated with the diverse types and stages of cancer. Obtusilactone B is a butanolide derivative purified from Machilus thunbergii. In this study, we show that obtusilactone B functions as a small-molecule inhibitor that causes abnormal nuclear envelope dynamics and inhibits growth by suppressing vaccinia-related kinase 1 (VRK1)-mediated phosphorylation of barrier-to-autointegration factor (BAF). BAF is important in maintaining lamin integrity, which is closely associated with diseases that include cancer. Specific binding of obtusilactone B to BAF suppressed VRK1-mediated BAF phosphorylation and the subsequent dissociation of the nuclear envelope from DNA that allows cells to progress through the cell cycle. Obtusilactone B potently induced tumor cell death in vitro, indicating that specific targeting of BAF to block cell cycle progression can be an effective anticancer strategy. Our results demonstrate that targeting a major constituent of the nuclear envelope may be a novel and promising alternative approach to cancer treatment.</P>
Macro Histone H2A1.2 (MacroH2A1) Protein Suppresses Mitotic Kinase VRK1 during Interphase
Kim, Wanil,Chakraborty, Goutam,Kim, Sangjune,Shin, Joon,Park, Choon-Ho,Jeong, Min-Woo,Bharatham, Nagakumar,Yoon, Ho Sup,Kim, Kyong-Tai American Society for Biochemistry and Molecular Bi 2012 The Journal of biological chemistry Vol.287 No.8
Kim, Seong-Hoon,Lyu, Ha-Na,Kim, Ye Seul,Jeon, Yong Hyun,Kim, Wanil,Kim, Sangjune,Lim, Jong-Kwan,Lee, Ho Won,Baek, Nam-In,Choi, Kwan-Yong,Lee, Jaetae,Kim, Kyong-Tai American Society for Pharmacology and Experimental 2015 The Journal of Pharmacology and Experimental Thera Vol.352 No.1
<P>To date, many anticancer drugs have been developed by directly or indirectly targeting microtubules, which are involved in cell division. Although this approach has yielded many anticancer drugs, these drugs produce undesirable side effects. An alternative strategy is needed, and targeting mitotic exit may be one alternative approach. Localization of phosphorylated barrier-to-autointegration factor (BAF) to the chromosomal core region is essential for nuclear envelope compartment relocalization. In this study, we isolated brazilin from Caesalpinia sappan Leguminosae and demonstrated that it inhibited BAF phosphorylation in vitro and in vivo. Moreover, we demonstrated direct binding between brazilin and BAF. The inhibition of BAF phosphorylation induced abnormal nuclear envelope reassembly and cell death, indicating that perturbation of nuclear envelope reassembly could be a novel approach to anticancer therapy. We propose that brazilin isolated from C. sappan may be a new anticancer drug candidate that induces cell death by inhibiting vaccinia-related kinase 1-mediated BAF phosphorylation.</P>
Nonthermal-plasma-mediated animal cell death
Kim, Wanil,Woo, Kyung-Chul,Kim, Gyoo-Cheon,Kim, Kyong-Tai Institute of Physics [etc.] 2011 Journal of Physics. D, Applied Physics Vol.44 No.1
<P>Animal cell death comprising necrosis and apoptosis occurred in a well-regulated manner upon specific stimuli. The physiological meanings and detailed molecular mechanisms of cell death have been continuously investigated over several decades. Necrotic cell death has typical morphological changes, such as cell swelling and cell lysis followed by DNA degradation, whereas apoptosis shows blebbing formation and regular DNA fragmentation. Cell death is usually adopted to terminate cancer cells <I>in vivo</I>. The current strategies against tumour are based on the induction of cell death by adopting various methods, including radiotherapy and chemotherapeutics. Among these, radiotherapy is the most frequently used treatment method, but it still has obvious limitations. Recent studies have suggested that the use of nonthermal air plasma can be a prominent method for inducing cancer cell death. Plasma-irradiated cells showed the loss of genomic integrity, mitochondrial dysfunction, plasma membrane damage, etc. Tumour elimination with plasma irradiation is an emerging concept in cancer therapy and can be accelerated by targeting certain tumour-specific proteins with gold nanoparticles. Here, some recent developments are described so that the mechanisms related to plasma-mediated cell death and its perspectives in cancer treatment can be understood.</P>
[차량운동성능부문] ADAMS를 이용한 Active Height Control System이 장착된 Sport Utility Vehicle의 조종안정성 해석
김완일(Wanil Kim),이정우(JeongWoo Lee),김학균(HaakKyun Kim),두민수(MinSoo Doo),김효석(HyoSeok Kim),도원주(WonJoo Doh) 한국자동차공학회 2001 한국자동차공학회 춘 추계 학술대회 논문집 Vol.2001 No.11_2
In this paper we propose an Active Height Control system which consists of an automatic air leveling and semiactive suspension system for an SUV (sport utility vehicle). Prior to a real car installation to estimate the vehicle performance and tune the control logic, we model the vehicle with flexible body frame and AHC system using ADAMS. We analyzed the vehicle handling performance for various driving conditions by simulation. Then we apply the AHC system to an SUV and tested its performances.
Kim, Sangjune,Park, Do-Young,Lee, Dohyun,Kim, Wanil,Jeong, Young-Hun,Lee, Juhyun,Chung, Sung-Kee,Ha, Hyunjung,Choi, Bo-Hwa,Kim, Kyong-Tai American Society for Microbiology 2014 Molecular and cellular biology Vol.34 No.4
<P>Misfolding of proteins containing abnormal expansions of polyglutamine (polyQ) repeats is associated with cytotoxicity in several neurodegenerative disorders, including Huntington's disease. Recently, the eukaryotic chaperonin TRiC hetero-oligomeric complex has been shown to play an important role in protecting cells against the accumulation of misfolded polyQ protein aggregates. It is essential to elucidate how TRiC function is regulated to better understand the pathological mechanism of polyQ aggregation. Here, we propose that vaccinia-related kinase 2 (VRK2) is a critical enzyme that negatively regulates TRiC. In mammalian cells, overexpression of wild-type VRK2 decreased endogenous TRiC protein levels by promoting TRiC ubiquitination, but a VRK2 kinase-dead mutant did not. Interestingly, VRK2-mediated downregulation of TRiC increased aggregate formation of a polyQ-expanded huntingtin fragment. This effect was ameliorated by rescue of TRiC protein levels. Notably, small interference RNA-mediated knockdown of VRK2 enhanced TRiC protein stability and decreased polyQ aggregation. The VRK2-mediated reduction of TRiC protein levels was subsequent to the recruitment of COP1 E3 ligase. Among the members of the COP1 E3 ligase complex, VRK2 interacted with RBX1 and increased E3 ligase activity on TRiC <I>in vitro</I>. Taken together, these results demonstrate that VRK2 is crucial to regulate the ubiquitination-proteosomal degradation of TRiC, which controls folding of polyglutamine proteins involved in Huntington's disease.</P>
Kim, Yonggi,Kim, Hyeon Ji,Cho, Wanil,Ko, Sanghoon,Park, Sung Kwon,Lee, Suyong Food & Nutrition Press 2017 Journal of texture studies Vol.48 No.5
<P>Practical applicationsAs the elderly population is increasing throughout the world, there are growing interests in developing food products for older adults with difficulties in chewing and swallowing in the food industry. In this study, the instrumental texture of solid foods in a starch gel system was correlated with the sensory properties perceived by the people aged 60 and older. Based on the principal component analysis, the corn starch gel samples with different hardness were classified into the five groups that were presented with the ranges of stress values. The results obtained in this study may thus provide valuable information on the standard criteria and guidelines customized for the elderly.</P>