• Title/Summary/Keyword: Target degradation

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CYP1B1 Activates Wnt/β-Catenin Signaling through Suppression of Herc5-Mediated ISGylation for Protein Degradation on β-Catenin in HeLa Cells

  • Park, Young-Shin;Kwon, Yeo-Jung;Chun, Young-Jin
    • Toxicological Research
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    • v.33 no.3
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    • pp.211-218
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    • 2017
  • Cytochrome P450 1B1 (CYP1B1) acts as a hydroxylase for estrogen and activates potential carcinogens. Moreover, its expression in tumor tissues is much higher than that in normal tissues. Despite this association between CYP1B1 and cancer, the detailed molecular mechanism of CYP1B1 on cancer progression in HeLa cells remains unknown. Previous reports indicated that the mRNA expression level of Herc5, an E3 ligase for ISGylation, is promoted by CYP1B1 suppression using specific small interfering RNA, and that ISGylation may be involved in ubiquitination related to ${\beta}-catenin$ degradation. With this background, we investigated the relationships among CYP1B1, Herc5, and ${\beta}-catenin$. RT-PCR and western blot analyses showed that CYP1B1 overexpression induced and CYP1B1 inhibition reduced, respectively, the expression of $Wnt/{\beta}-catenin$ signaling target genes including ${\beta}-catenin$ and cyclin D1. Moreover, HeLa cells were treated with the CYP1B1 inducer $7,12-dimethylbenz[{\alpha}]anthracene$ (DMBA) or the CYP1B1 specific inhibitor, tetramethoxystilbene (TMS) and consequently DMBA increased and TMS decreased ${\beta}-catenin$ and cyclin D1 expression, respectively. To determine the correlation between CYP1B1 expression and ISGylation, the expression of ISG15, a ubiquitin-like protein, was detected following CYP1B1 regulation, which revealed that CYP1B1 may inhibit ISGylation through suppression of ISG15 expression. In addition, the mRNA and protein expression levels of Herc5 were strongly suppressed by CYP1B1. Finally, an immunoprecipitation assay revealed a direct physical interaction between Herc5 and ${\beta}-catenin$ in HeLa cells. In conclusion, these data suggest that CYP1B1 may activate $Wnt/{\beta}-catenin$ signaling through stabilization of ${\beta}-catenin$ protein from Herc5-mediated ISGylation for proteosomal degradation.

Isolation, Identification and Use of Bacterial Strain Ochrobactrum intermedium PDB-3 for Degradation of the Pesticide Chlorpyrifos

  • Diyorbek Kosimov;Lyudmila Zaynitdinova;Aziza Mavjudova;Muzaffar Muminov;Oybek Shukurov
    • Microbiology and Biotechnology Letters
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    • v.52 no.1
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    • pp.44-54
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    • 2024
  • One of the serious modern environmental problems is pollution caused by highly toxic pesticides. Only small amounts of applied pesticides reach their target, and the rest ends up in soil and water. Chlorpyrifos is a toxic, broad-spectrum organophosphate insecticide. In humans, chlorpyrifos inhibits acetylcholinesterase (AChE) in the peripheral and central nervous system, and particularly in children, small amounts of this pesticide cause neurotoxic damage. As the toxic effects of chlorpyrifos and its persistence in the environment require its removal from contaminated sites, it is essential to study the biological diversity of chlorpyrifos-degrading microorganisms. In this study, we sought to determine the chlorpyrifos-degrading ability of the bacterial strain Ochrobactrum intermedium PDB-3. This strain was isolated from soil contaminated with various pesticides and identified as PDB-3 based on morpho-cultural characteristics, MALDI-TOF MS, and 16S rRNA. Studies were conducted for 30 days in sterile soils containing initial concentrations of 50, 75, 100, and 125 mg/kg of chlorpyrifos. To determine the degradation of chlorpyrifos, a liquid culture of the strain was added to the soil at three optical densities: 0, and after 24 and 48 h (OD = 0.03, 0.2 and 0.32). Using GX-MS, we determined that chlorpyrifos was converted to 3,5,6-trichloro-2-pyridinol (TCP). We also found that with increasing optical density, rapid degradation of the initial concentration of chlorpyrifos occurred. Sterile soil without strain PDB-3 was used as a control sample.

A Novel Two-step Channel Prediction Technique for Adaptive Transmission in OFDM/FDD System (OFDM/FDD 시스템에서 Target QoS 만족을 위한 다단계 적응전송 채널예측기법)

  • Heo Joo;Chang Kyung-Hi
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.31 no.8A
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    • pp.745-751
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    • 2006
  • The transmitter requires knowledge of the channel status information in order to adopt the adaptive modulation and coding scheme(AMC) for OFDM system. But in the outdoor environment which the users have high mobility, the channel status information from the users is outdated, so that it induces the degradation of system throughput and packet error rate(PER) performance. To solve this problem, researches about applying channel prediction technique to the AMC scheme have been proceeded. Most channel prediction techniques assume that there is no channel variation in the predefined time duration, e.g., a slot. As a result, those techniques cannot compensate the degradation of PER performance resulting from the rapid variation of channel during the slot duration. This paper introduces a novel channel prediction technique for OFDM/FDD system to support adaptive modulation and coding scheme over rapidly time-varying multipath fading channel. The proposed channel prediction technique considers the time-varying nature of channel during the slot duration. Simulation results show that the AMC scheme of OFDM/FDD system utilizing the proposed channel prediction technique can guarantee the target PER of 1% without any loss of system throughput compared with the case supported by the conventional channel prediction under ITU-R Veh A 30km/h.

Development of maintenance cost estimation method considering bridge performance changes (교량 성능변화를 고려한 유지관리비용 추계분석 방법 개발)

  • Sun, Jong-Wan;Lee, Huseok;Park, Kyung-Hoon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.19 no.12
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    • pp.717-724
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    • 2018
  • To prepare for the explosive increase in maintenance costs of bridges according to the aging of infrastructure, future maintenance costs of bridges should be predicted. For this purpose, the management status of bridges was investigated and modeled as the upper limit of the performance level and the target management level according to the life cycle. This paper proposes methodologies and procedures for estimating the bridge maintenance costs using two models and existing cost and performance prediction models that consist of unit repair cost model according to the safety score, performance degradation model of bridges, unit reconstruction cost, and average reconstruction time. To verify the applicability, future maintenance costs can be forecasted for specific management agency considering the number of bridges, degree of aging, and current management status. As a result, it is possible to obtain the maintenance cost and safety level of an individual bridge level for each year. In addition, by summing them up to the agency level, the average safety score, ratio of the safety level, inspection costs, repair costs, and reconstruction costs can be obtained. In a further study, the changes in maintenance costs can be analyzed according to the changes in the target management levels using the developed method. The optimal management level can be suggested by reviewing the results.

Formation Temperature Dependence of Thermal Stability of Nickel Silicide with Ni-V Alloy for Nano-scale MOSFETs

  • Tuya, A.;Oh, S.Y.;Yun, J.G.;Kim, Y.J.;Lee, W.J.;Ji, H.H.;Zhang, Y.Y.;Zhong, Z.;Lee, H.D.
    • Proceedings of the IEEK Conference
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    • 2005.11a
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    • pp.611-614
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    • 2005
  • In this paper, investigated is the relationship between the formation temperature and the thermal stability of Ni silicide formed with Ni-V (Nickel Vanadium) alloy target. The sheet resistance after the formation of Ni silicide with the Ni-V showed stable characteristic up to RTP temperature of $700\;^{\circ}C$ while degradation of sheet resistance started at that temperature in case of pure-Ni. Moreover, the Ni silicide with Ni-V indicated more thermally stable characteristic after the post-silicidation annealing. It is further found that the thermal robustness of Ni silicide with Ni-V was highly dependent on the formation temperature. With the increased silicidation temperature (around $700\;^{\circ}C$), the more thermally stable Ni silicide was formed than that of low temperature case using the Ni-V.

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Oxidation of Chloroethenes by Heat-Activated Persulfate (과황산의 열적활성화 및 염소계용제의 산화분해)

  • Zhang, Hailong;Kwon, Hee-Won;Choi, Jeong-Hak;Kim, Young-Hun
    • Journal of Environmental Science International
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    • v.26 no.11
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    • pp.1201-1208
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    • 2017
  • Oxidative degradation of chlorinated ethenes was carried out using heat-activated persulfate. The activation rate of persulfate was dependent on the temperature and the activation reaction rate could be explained based on the Arrhenius equation. The activation energy of persulfate was 19.3 kcal/mol under the assumption that the reaction between the sulfate radical and tricholoroethene (TCE) is very fast. Activation could be achieved at a moderate temperature, so that the adverse effects due to high temperature in the soil environment were mitigated. The reaction rate of TCE was directly proportional to the concentration of persulfate, indicating that the remediation rate can be controlled by the concentration of the injected persulfate. The solution was acidized after the oxidation, and this was dependent on the oxidation temperature. The consumption rate of persulfate was high in the presence of the target organic, but the self-decomposition rate became very low as the target was completely removed.

Ex-situ Reductive Dechlorination of Carbon Tetrachloride by Iron Sulfide in Batch Reactor

  • Choi, Kyung-Hoon;Lee, Woo-Jin
    • Environmental Engineering Research
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    • v.13 no.4
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    • pp.177-183
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    • 2008
  • Ex-situ reductive dechlorination of carbon tetrachloride (CT) by iron sulfide in a batch reactor was characterized in this study. Reactor scaled-up by 3.5 L was used to investigate the effect of reductant concentration on removal efficiency and process optimization for ex-situ degradation. The experiment was conducted by using both liquid-phase and gas-phase volume at pH 8.5 in anaerobic condition. For 1 mM of initial CT concentration, the removal of the target compound was 98.9% at 6.0 g/L iron sulfide. Process optimization for ex-situ treatment was performed by checking the effect of transition metal and mixing time on synthesizing iron sulfide solution, and by determining of the regeneration time. The effect of Co(II) as transition metal was shown that the reaction rate was slightly improved but the improvement was not that outstanding. The result of determination on the regeneration time indicated that regenerating reductant capacity after $1^{st}$ treatment of target compound was needed. Due to the high removal rates of CT, ex-situ reductive dechlorination in batch reactor can be used for basic treatment for the chlorinated compounds.

Implications of NQO1 in cancer therapy

  • Oh, Eun-Taex;Park, Heon Joo
    • BMB Reports
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    • v.48 no.11
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    • pp.609-617
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    • 2015
  • NAD(P)H:quinone oxidoreductase (NQO1), an obligatory two-electron reductase, is a ubiquitous cytosolic enzyme that catalyzes the reduction of quinone substrates. The NQO1- mediated two-electron reduction of quinones can be either chemoprotection/detoxification or a chemotherapeutic response, depending on the target quinones. When toxic quinones are reduced by NQO1, they are conjugated with glutathione or glucuronic acid and excreted from the cells. Based on this protective effect of NQO1, the use of dietary compounds to induce the expression of NQO1 has emerged as a promising strategy for cancer prevention. On the other hand, NQO1-mediated two-electron reduction converts certain quinone compounds (such as mitomycin C, E09, RH1 and β-lapachone) to cytotoxic agents, leading to cell death. It has been known that NQO1 is expressed at high levels in numerous human cancers, including breast, colon, cervix, lung, and pancreas, as compared with normal tissues. This implies that tumors can be preferentially damaged relative to normal tissue by cytotoxic quinone drugs. Importantly, NQO1 has been shown to stabilize many proteins, including p53 and p33ING1b, by inhibiting their proteasomal degradation. This review will summarize the biological roles of NQO1 in cancer, with emphasis on recent findings and the potential of NQO1 as a therapeutic target for the cancer therapy.

siRNA Mediated Silencing of NIN1/RPN12 Binding Protein 1 Homolog Inhibits Proliferation and Growth of Breast Cancer Cells

  • Huang, Wei-Yi;Chen, Dong-Hui;Ning, Li;Wang, Li-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1823-1827
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    • 2012
  • The gene encoding the Nin one binding (NOB1) protein which plays an essential role in protein degradation has been investigated for possible tumor promoting functions. The present study was focused on NOB1 as a possible therapeutic target for breast cancer treatment. Lentivirus mediated NOB1 siRNA transfection was used to silence the NOB1 gene in two established breast cancer cell lines, MCF-7 and MDA-MB-231, successful transfection being confirmed by fluorescence imaging. NOB1 deletion caused significant decline in cell proliferation was observed in both cell lines as investigated by MTT assay. Furthermore the number and size of the colonies formed were also significantly reduced in the absence of NOB1. Moreover NOB1 gene knockdown arrested the cell cycle and inhibited cell cycle related protein expression. Collectively these results indicate that NOB1 plays an essential role in breast cancer cell proliferation and its gene expression could be a therapeutic target.

Structural Basis of the Disease-related Proteins: Target Oriented Structural Proteomics

  • Jinho Moon;Heo, Yong-Suk;Kim, Young-Kwan;Kim, Hye-Yeon;Park, Min-Hye;Hwang, Kwang-Yeon
    • Proceedings of the Korea Crystallographic Association Conference
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    • 2003.05a
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    • pp.15-15
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    • 2003
  • To discover new drugs more quickly and more efficiently, pharmaceutical companies and biotechnology firms are increasingly turning to the genomics and the structural proteomics technologies. Structural-proteomics can provide a foundation for this through the determination and analysis for protein structure on a genomics scale. Among many structures determined by CGI, we will present with the representative examples drawn from our work on novel structures or complex structures of the disease-related proteins. The alpha subunit of Hypoxia-inducible factor (HIF) is targeted for degradation under normoxic conditions by an ubiquitin-ligase complex that recognizes a hydroxylated proline residue in HIF. Hydroxylation is catalysed by HIF prolyl 4-hydroxylases (HIFPH) which are fe(II) and 2-oxoglutarate (2-OG) dependent oxygenases. Here, we discuss the first crystal structure of the catalytic domain of HIFPH in complexes, with the Fe(II)/2-OG at 1.8Å. These structures suggest that the Ll region (residues 236-253), which is also conserved in mammals, form a 'lid' that closes over the active site. The structural and mutagenesis analyses allow us to provide a focus for understanding cellular responses to hypoxia and a target for the therapeutic manipulation.

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