• Title/Summary/Keyword: Target degradation

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Aryl Sulfonamides Induce Degradation of Aryl Hydrocarbon Receptor Nuclear Translocator through CRL4DCAF15 E3 Ligase

  • Kim, Sung Ah;Jo, Seung-Hyun;Cho, Jin Hwa;Yu, Min Yeong;Shin, Ho-Chul;Kim, Jung-Ae;Park, Sung Goo;Park, Byoung Chul;Kim, Sunhong;Kim, Jeong-Hoon
    • Molecules and Cells
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    • v.43 no.11
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    • pp.935-944
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    • 2020
  • Aryl hydrocarbon receptor nuclear translocator (ARNT) plays an essential role in maintaining cellular homeostasis in response to environmental stress. Under conditions of hypoxia or xenobiotic exposure, ARNT regulates the subset of genes involved in adaptive responses, by forming heterodimers with hypoxia-inducible transcription factors (HIF1α and HIF2α) or aryl hydrocarbon receptor (AhR). Here, we have shown that ARNT interacts with DDB1 and CUL4-associated factor 15 (DCAF15), and the aryl sulfonamides, indisulam and E7820, induce its proteasomal degradation through Cullin-RING finger ligase 4 containing DCAF15 (CRL4DCAF15) E3 ligase. Moreover, the two known neo-substrates of aryl sulfonamide, RNA-binding motif protein 39 (RBM39) and RNA-binding motif protein 23 (RBM23), are not required for ARNT degradation. In line with this finding, aryl sulfonamides inhibited the transcriptional activities of HIFs and AhR associated with ARNT. Our results collectively support novel regulatory roles of aryl sulfonamides in both hypoxic and xenobiotic responses.

Purification, crystallization, and preliminary X-ray diffraction data analysis for PB1 dimer of P62/SQSTM1

  • Shin, Ho-Chul;Lim, Dahwan;Ku, Bonsu;Kim, Seung Jun
    • Biodesign
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    • v.6 no.4
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    • pp.100-102
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    • 2018
  • Autophagy is a degradation pathway that targets many cellular components and plays a particularly important role in protein degradation and recycling. This process is very complex and several proteins participate in this process. One of them, P62/SQSTM1, is related to the N-end rule and induces protein degradation through autophagy. The P62/SQSTM1 makes a huge oligomer, and this oligomerization is known to play an important role in its mechanism. This oligomerization takes two steps. First, the PB1 domain of P62/SQSTM1 makes the base oligomer, and then, when the ligand binds to the ZZ domain of P62/SQSTM1, it induces a higher oligomer by the disulfide bond of the two cysteines. To understand the oligomerization mechanism of P62/SQSTM1, we need to know the dimerization of the PB1 domain. In this study, crystals of PB1 dimer were made and the crystals were diffracted by X-ray to collect usable data up to 3.2A. We are analyzing the structure using the molecular replacement (MR) method.

Degradation of Volatile Hydrocarbons Using Continuous-Flow Photocatalytic Systems with Enhanced Catalytic Surface Areas

  • Jo, Wan-Kuen;Yang, Sung-Hoon;Shin, Seung-Ho;Yang, Sung-Bong
    • Environmental Engineering Research
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    • v.16 no.2
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    • pp.91-96
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    • 2011
  • Limited information is available on the degradation of volatile hydrocarbons determined via the use of plate-inserted photocatalytic reactors. This has led to the evaluation of surface areas of cylindrical continuous-flow photocatalytic reactors for the degradation of three selected aromatic hydrocarbons. Three types of reactors were prepared: a double cylinder-type, a single cylindrical-type without plates and a single cylindrical-type with inserted glass tubes. According to diffuse reflectance, FTIR and X-ray diffraction (XRD) spectroscopy, the surface characteristics of a coated photocatalyst were very similar to those of raw $TiO_2$, thereby suggesting that the coated photocatalyst exhibited the same photocatalytic activity as the raw $TiO_2$. The photocatalytic degradation efficiencies were significantly or slightly higher for the single cylinder-type reactor than for the double cylinder-type reactor which had a greater catalytic surface area. However, for all target compounds, the degradation efficiencies increased gradually when the number of plates was increased. Accordingly, it was suggested that the surface area being enhanced for the plate-inserted reactor would elevate the photocatalytic degradation efficiency effectively. In addition, this study confirmed that both initial concentrations of target compounds and flow rates were important parameters for the photocatalytic removal mechanism of these plate-inserted photocatalytic reactors.

MicroRNA-directed cleavage of targets: mechanism and experimental approaches

  • Park, June Hyun;Shin, Chanseok
    • BMB Reports
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    • v.47 no.8
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    • pp.417-423
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    • 2014
  • MicroRNAs (miRNAs) are a large family of post-transcriptional regulators, which are 21-24 nt in length and play a role in a wide variety of biological processes in eukaryotes. The past few years have seen rapid progress in our understanding of miRNA biogenesis and the mechanism of action, which commonly entails a combination of target degradation and translational repression. The target degradation mediated by Argonaute-catalyzed endonucleolytic cleavage exerts a significant repressive effect on target mRNA expression, particularly during rapid developmental transitions. This review outlines the current understanding of the mechanistic aspects of this important process and discusses several different experimental approaches to identify miRNA cleavage targets.

Degradation of thin carbon-backed lithium fluoride targets bombarded by 68 MeV 17O beams

  • Y.H. Kim;B. Davids;M. Williams;K.H. Hudson;S. Upadhyayula;M. Alcorta;P. Machule;N.E. Esker;C.J. Griffin;J. Williams;D. Yates;A. Lennarz;C. Angus;G. Hackman;D.G. Kim;J. Son;J. Park;K. Pak;Y.K. Kim
    • Nuclear Engineering and Technology
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    • v.55 no.3
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    • pp.919-926
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    • 2023
  • To analyze the cause of the destruction of thin, carbon-backed lithium fluoride targets during a measurement of the fusion of 7Li and 17O, we estimate theoretically the lifetimes of carbon and LiF films due to sputtering, thermal evaporation, and lattice damage and compare them with the lifetime observed in the experiment. Sputtering yields and thermal evaporation rates in carbon and LiF films are too low to play significant roles in the destruction of the targets. We estimate the lifetime of the target due to lattice damage of the carbon backing and the LiF film using a previously reported model. In the experiment, elastically scattered target and beam ions were detected by surface silicon barrier (SSB) detectors so that the product of the beam flux and the target density could be monitored during the experiment. The areas of the targets exposed to different beam intensities and fluences were degraded and then perforated, forming holes with a diameter around the beam spot size. Overall, the target thickness tends to decrease linearly as a function of the beam fluence. However, the thickness also exhibits an increasing interval after SSB counts per beam ion decreases linearly, extending the target lifetime. The lifetime of thin LiF film as determined by lattice damage is calculated for the first time using a lattice damage model, and the calculated lifetime agrees well with the observed target lifetime during the experiment. In experiments using a thin LiF target to induce nuclear reactions, this study suggests methods to predict the lifetime of the LiF film and arrange the experimental plan for maximum efficiency.

Silymarin-Mediated Degradation of c-Myc Contributes to the Inhibition of Cell Proliferation in Human Colorectal Cancer Cells

  • Eo, Hyun Ji;Jeong, Jin Boo;Koo, Jin Suk;Jeong, Hyung Jin
    • Korean Journal of Plant Resources
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    • v.30 no.3
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    • pp.265-271
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    • 2017
  • In this study, we elucidated the molecular mechanism of silymarin by which silymarin may inhibits cell proliferation in human colorectal cancer cells in order to search the new potential anti-cancer target associated with the cell growth arrest. Silymarin reduced the level of c-Myc protein but not mRNA level indicating that silymarin-mediated downregulation of c-Myc may result from the proteasomal degradation. In the confirmation of silymarin-mediated c-Myc degradation, MG132 as a proteasome inhibitor attenuated c-Myc degradation by silymarin. In addition, silymarin phosphorylated the threonine-58 (Thr58) of c-Myc and the point mutation of Thr58 to alanine blocked its degradation by silymarin, which indicates that Thr58 phosphorylation may be an important modification for silymarin-mediated c-Myc degradation. We observed that the inhibition of ERK1/2, p38 and $GSK3{\beta}$ blocked the Thr58 phosphorylation and subsequent c-Myc degradation by silymarin. Finally, the point mutation of Thr58 to alanine attenuated silymarin-mediated inhibition of the cell growth. The results suggest that silymarin induces the cell growth arrest through c-Myc proteasomal degradation via ERK1/2, p38 and $GSK3{\beta}-dependent$ Thr58 phosphorylation.

Degradation characteristics and reaction pathways of tetracycline by ferrate(VI) in various aqueous conditions (Ferrate(VI)를 이용한 다양한 수중 환경에서의 tetracycline의 분해 특성 및 반응 경로 연구)

  • Park, Kyeong-Deok;Kim, Il-Kyu
    • Journal of Korean Society of Water and Wastewater
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    • v.35 no.1
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    • pp.27-37
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    • 2021
  • Tetracycline is one of the most commonly used as antibiotics for the livestock industry and it is still widely used nowadays. Tetracycline and its metabolites are excreted with excrement, which is difficult to completely removed with conventional sewage treatment, therefore it is apprehended that the tetracycline-resistant bacteria occurs. In this study, the oxidant named ferrate(VI) was used to degrade the tetracycline and investigate the reaction between ferrate(VI) and tetracycline under various aqueous conditions. The highest degradation efficiency of tetracycline occurred in basic condition (pH 10.1 ± 0.1) because of the pKa values of tetracycline and ferrate(VI). The results also showed the effect of water temperature on the degradation of tetracycline was not significant. In addition, the dosage of ferrate(VI) was higher, the degradation of tetracycline and the self-degradation of ferrate(VI) also higher, finally the efficiency of ferrate(VI) was lower. The results said that the various mechanisms effects the reaction of ferrate(VI) oxidation, it required the consideration of the characteristics of the target compound for optimal degradation efficiency. Additionally, intermediate products were detected with LC/MS/MS and three degradation pathways were proposed.

Photodegradation of Volatile Organic Compound (VOC) Through V-Doped or CuOx-grafted $TiO_2$ nanoparticles

  • Kim, Beum Woo;Kim, Seonmin
    • Proceedings of the Korean Vacuum Society Conference
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    • 2013.08a
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    • pp.271.1-271.1
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    • 2013
  • Titania is usually used in sun-screens, tooth paste, and other daily used objects as a pigment. However, scientists have focused on titania as photocatalyst due to its excellent activities. By fabricating vanadium doped TiO2 and CuOx co-catalyzed TiO2 nano-size filter, the degradation level of the volatile organic compound (VOC) concentration was tested using 365nm UV LED as light source in a closed chamber. Main purpose for this test is to evaluate the activities of various catalysts for degrading the VOCs which are detrimental to human body and toluene and p-xylene were chosen in the VOC removal test. Target gas materials were injected into the test chamber with dry air as carrier gas which was flowed into the gas washer bottle filled with liquid form of VOC substance. When the VOC gas flows into the chamber, it is circulated by 200 mm fan in order to contact with the set-up filter on the aluminum holder. Target gas concentration in the chamber was monitored using VOC detector (miniRae3000, Raesystems) which was also placed inside the chamber. With the measured concentration, the VOC degradation efficiency and the degradation rate were evaluated and used to compare the catalytic activities.

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Design of a Flexible Planar RFID Tag Antenna with Low Performance Degradation from Nearby Target Objects

  • Choo, Jae-Yul;Ryoo, Jeong-Ki;Choo, Ho-Sung
    • Journal of electromagnetic engineering and science
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    • v.11 no.1
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    • pp.1-4
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    • 2011
  • In this letter, we propose a novel tag antenna that has low performance degradation with nearby dielectric material. We obtained a stable reading performance and a broad matching bandwidth on nearby dielectric materials by employing a T-matching network with thick line width and capacitively slot-loaded arms. We then built the proposed antenna and measured the tag sensitivity to examine the reading characteristics with nearby dielectric materials. The measured results clearly demonstrate stable tag sensitivity with various nearby dielectric materials, such as foam, acrylic-plastic, glass, and ceramic plates. To more closely observe the antenna characteristics with nearby dielectric materials, we also examined the impedance variation and surface current distribution with respect to the dielectric constant of nearby target objects, which ranged from $1{\times}{\varepsilon}_0$ to $16{\times}{\varepsilon}_0$.

Crosstalk between RNA silencing and RNA quality control in plants

  • Yun Ju Kim
    • BMB Reports
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    • v.56 no.6
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    • pp.321-325
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    • 2023
  • RNAs are pivotal molecules acting as messengers of genetic information and regulatory molecules for cellular development and survival. From birth to death, RNAs face constant cellular decision for the precise control of cellular function and activity. Most eukaryotic cells employ conserved machineries for RNA decay including RNA silencing and RNA quality control (RQC). In plants, RQC monitors endogenous RNAs and degrades aberrant and dysfunctional species, whereas RNA silencing promotes RNA degradation to repress the expression of selected endogenous RNAs or exogenous RNA derived from transgenes and virus. Interestingly, emerging evidences have indicated that RQC and RNA silencing interact with each by sharing target RNAs and regulatory components. Such interaction should be tightly organized for proper cellular survival. However, it is still elusive that how each machinery specifically recognizes target RNAs. In this review, we summarize recent advances on RNA silencing and RQC pathway and discuss potential mechanisms underlying the interaction between the two machineries.