• BMB Reports
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• v.52 no.3
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• pp.163-164
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• 2019

The ribosomal synthesis of proteins in the eukaryotic cytosol has always been thought to start from the unformylated N-terminal (Nt) methionine (Met). In contrast, in virtually all nascent proteins in bacteria and eukaryotic organelles, such as mitochondria and chloroplasts, Nt-formyl-methionine (fMet) is the first building block of ribosomal synthesis. Through extensive approaches, including mass spectrometric analyses of the N-termini of proteins and molecular genetic techniques with an affinity-purified antibody for Nt-formylation, we investigated whether Nt-formylated proteins could also be produced and have their own metabolic fate in the cytosol of a eukaryote, such as yeast Saccharomyces cerevisiae. We discovered that Nt-formylated proteins could be generated in the cytosol by yeast mitochondrial formyltransferase (Fmt1). These Nt-formylated proteins were massively upregulated in the stationary phase or upon starvation for specific amino acids and were crucial for the adaptation to specific stresses. The stress-activated kinase Gcn2 was strictly required for the upregulation of Nt-formylated proteins by regulating the activity of Fmt1 and its retention in the cytosol. We also found that the Nt-fMet residues of Nt-formylated proteins could be distinct N-terminal degradation signals, termed fMet/N-degrons, and that Psh1 E3 ubiquitin ligase mediated the selective destruction of Nt-formylated proteins as the recognition component of a novel eukaryotic fMet/N-end rule pathway, termed fMet/N-recognin.

• BMB Reports
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• v.57 no.7
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• pp.318-323
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• 2024

Regulation of cell fate and lung cell differentiation is associated with Aminoacyl-tRNA synthetases (ARS)-interacting multifunctional protein 2 (AIMP2), which acts as a non-enzymatic component required for the multi-tRNA synthetase complex. In response to DNA damage, a component of AIMP2 separates from the multi-tRNA synthetase complex, binds to p53, and prevents its degradation by MDM2, inducing apoptosis. Additionally, AIMP2 reduces proliferation in TGF-β and Wnt pathways, while enhancing apoptotic signaling induced by tumor necrosis factor-α. Given the crucial role of these pathways in tumorigenesis, AIMP2 is expected to function as a broad-spectrum tumor suppressor. The full-length AIMP2 transcript consists of four exons, with a small section of the pre-mRNA undergoing alternative splicing to produce a variant (AIMP2-DX2) lacking the second exon. AIMP2-DX2 binds to FBP, TRAF2, and p53 similarly to AIMP2, but competes with AIMP2 for binding to these target proteins, thereby impairing its tumor-suppressive activity. AIMP2-DX2 is specifically expressed in a diverse range of cancer cells, including breast cancer, liver cancer, bone cancer, and stomach cancer. There is growing interest in AIMP2-DX2 as a promising biomarker for prognosis and diagnosis, with AIMP2-DX2 inhibition attracting significant interest as a potentially effective therapeutic approach for the treatment of lung, ovarian, prostate, and nasopharyngeal cancers.

• Proceedings of the KSEEG Conference
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• 2002.06a
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• pp.81-100
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• 2002

While most of regulatory communities in abroad recognize ' 'natural attenuation " to include degradation, dispersion, dilution, sorption (including precipitation and transformation), and volatilization as governing Processes, regulators prefer "degradation" because this mechanism destroys the contaminant of concern. Unfortunately, true degradation only applies to organic contaminants and short- lived radionuclides, and leaves most metals and long-lived radionuclides. The natural attenuation Processes may reduce the potential risk Posed by site contaminants in three ways: (i)contaminants could be converted to a less toxic form througy destructive processes such as biodegradation or abiotic transformations; (ii) potential exposure levels may be reduced by lowering concentrations (dilution and dispersion); and (iii) contaminant mobility and bioavailability may be reduced by sorption to geomedia. In this review, authors will focus will focul on "sorption" among the natural attenuation processes of hazardous inorganic contaminants including radionuclides. Note though that sorption and transformation processes of inorganic contaminants in the natural setting could be influenced by biotic activities but our discussion would limit only to geochemical reactions involved in the natural attenuation. All of the geochemical reactions have been studied in-depth by numerous researchers for many years to understand "retardation" process of contaminants in the geomedia. The most common approach for estimating retardation is the determination of distrubution coefficiendts ($K_{d}$) of contaminants using parametric or mechanistic models. As typocally used in fate and contaminant transport calculations such as predictive models of the natural attenuation, the $K_{d}$ is defined as the ratio of the contaminant concentration in the surrounding aqueous solution when the system is at equilibrium. Unfortunately, generic or default $K_{d}$ values can result in significant error when used to predict contaminant migration rate and to select a site remediation alternative. Thus, to input the best $K_{d}$ value in the contaminant transport model, it is essential that important geochemical processes affecting the transport should be identified and understood. Precipitation/dissolution and adsorption/desorption are considered the most important geochemical processes affecting the interaction of inorganic and radionuclide contaminants with geomedia at the near and far field, respectively. Most of contaminants to be discussed in this presentation are relatively immobile, i.e., have very high $K_{d}$ values under natural geochemical environments. Unfortunately, the obvious containment in a source area may not be good enough to qualify as monitored natural attenuation site unless owner demonstrate the efficacy if institutional controls that were put in place to protect potential receptors. In this view, natural attenuation as a remedial alternative for some of sites contaminated by hazardous-inorganic components is regulatory and public acceptance issues rather than scientific issue.

• IMMUNE NETWORK
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• v.11 no.3
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• pp.135-154
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• 2011

The great discovery of microRNAs (miRNAs) has revolutionized current cell biology and medical science. miRNAs are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region of specific messenger RNAs for degradation or translational repression. New members of the miRNA family are being discovered on a daily basis and emerging evidence has demonstrated that miRNAs play a major role in a wide range of developmental process including cell proliferation, cell cycle, cell differentiation, metabolism, apoptosis, developmental timing, neuronal cell fate, neuronal gene expression, brain morphogenesis, muscle differentiation and stem cell division. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, psychiatric and neurological diseases, cardiovascular disease, and autoimmune disease. Interestingly, in addition, miRNA deficiencies or excesses have been correlated with a number of clinically important diseases ranging from cancer to myocardial infarction. miRNAs can repress the gene translation of hundreds of their targets and are therefore well-positioned to target a multitude of cellular mechanisms. As a consequence of extensive participation in normal functions, it is quite logical to ask the question if abnormalities in miRNAs should have importance in human diseases. Great discoveries and rapid progress in the past few years on miRNAs provide the hope that miRNAs will in the near future have a great potential in the diagnosis and treatment of many diseases. Currently, an explosive literature has focussed on the role of miRNA in human cancer and cardiovascular disease. In this review, I briefly summarize the explosive current studies about involvement of miRNA in various human cancers and cardiovascular disease.

• Korean Journal of Environmental Agriculture
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• v.15 no.4
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• pp.488-493
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• 1996

This study was conducted to find out the residual aspect and the effect of quizalofop-ethyl on microorganisms used to control broad-leaf weeds at Yeongok soil series, the experiment field, Chonnam R.D.A. and Namwon soil series, the experiment field, Jeju R.D.A. More than 60 percent of quizalofop-ethyl treated in soil was degraded within 7 days. The degradation of quizalofop-ethyl in soil increased rapidly with incubation temperature. The half-life of quizalofop-ethyl in soil was 15 days(Yeongok series) and 16 days(Namwon series). The number of microorganisms in soil treated with quizalofop-ethyl decreased prominently with incubation time. But the number of Fusarium did not reduce in comparison with that of other soil microorganisms. Therefore, it was thought that the decomposition of quizalofop-ethyl in soil was affected by $Fusarium^2$.

• Korean Journal of Environmental Agriculture
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• v.4 no.1
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• pp.1-5
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• 1985

Fate of tricyclazole in rice paddy system was studied. The effect on soil microorganism as well as the mutagenicity of the compound was also examined. The residues of tricyclazole in crops and soil with two times application before harvest were 0.37 in unpolished rice, 0.29 in polished rice, 0.14 in rice straw, and 0.15 ppm in paddy soil. With three times of application the residues were increased to 0.46, 0.39, and 0.19 ppm, respectively. Until $2{\sim}3$ weeks after treatment of pesticide the degradation of tricyclazole was progressed comparatively but very slowly afterward and the half life of that was about $140{\sim}180$ days. There was no effect for viable count of soil microorganisms and for mutagenic test by Salmonella and Saccharomyces systems.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.10a
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• pp.91-93
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• 2003

It has been estimated that the equivalent of approximately $US 50 billion has been spent on research on the behavior and fate of pesticides in the environment since Rachel Carson published “Silent Spring” in 1962. Much of the resulting knowledge has been summarized explicitly in computer algorithms in a variety of empirical, deterministic, and probabilistic simulation models. These models describe and predict the transport, degradation and resultant concentrations of pesticides in various compartments of the environment during and after application. In many cases the known errors of model predictions are large. For this reason they are typically designed to be “conservative”, i.e., err on the side of over-prediction of concentrations in order to err on the side of safety. These predictions are then compared with toxicity data, from tests of the pesticide on a series of standard representative biota, including terrestrial and aquatic indicator species and higher animals (e.g., wildlife and humans). The models' predictions are good enough in some cases to provide screening of those compounds which are very unlikely to do harm, and to indicate those compounds which must be investigated further. If further investigation is indicated a more detailed (and therefore more complicated) model may be employed to give a better estimate, or field experiments may be required. A model may be used to explore “what if” questions leading to possible alternative pesticide usage patterns which give lower potential environmental concentrations and allowable exposures. We are currently at a maturing stage in this research where the knowledge base of pesticide behavior in the environmental is growing more slowly than in the past. However, innovative uses are being made of the explosion in available computer technology to use models to take ever more advantage of the knowledge we have. In this presentation, current developments in the state of the art as practiced in North America and Europe will be presented. Specifically, we will look at the efforts of the ‘Focus’ consortium in the European Union, and the ‘EMWG’ consortium in North America. These groups have been innovative in developing a process and mechanisms for discussion amongst academic, agriculture, industry and regulatory scientists, for consensus adoption of research advances into risk management methodology.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.407-416
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• 2023

The regeneration of myocardium following acute circulatory events remains a challenge, despite numerous efforts. Mesenchymal stem cells (MSCs) present a promising cell therapy option, but their differentiation into cardiomyocytes is a time-consuming process. Although it has been demonstrated that PSME4 degrades acetyl-YAP1, the role of PSME4 in the cardiac commitment of MSCs has not been fully elucidated. Here we reported the novel role of PSME4 in MSCs cardiac commitment. It was found that overnight treatment with apicidin in primary-cultured mouse MSCs led to rapid cardiac commitment, while MSCs from PSME4 knock-out mice did not undergo this process. Cardiac commitment was also observed using lentivirus-mediated PSME4 knockdown in immortalized human MSCs. Immunofluorescence and Western blot experiments revealed that YAP1 persisted in the nucleus of PSME4 knockdown cells even after apicidin treatment. To investigate the importance of YAP1 removal, MSCs were treated with shYAP1 and apicidin simultaneously. This combined treatment resulted in rapid YAP1 elimination and accelerated cardiac commitment. However, overexpression of acetylation-resistant YAP1 in apicidin-treated MSCs impeded cardiac commitment. In addition to apicidin, the universal effect of histone deacetylase (HDAC) inhibition on cardiac commitment was confirmed using tubastatin A and HDAC6 siRNA. Collectively, this study demonstrates that PSME4 is crucial for promoting the cardiac commitment of MSCs. HDAC inhibition acetylates YAP1 and facilitates its translocation to the nucleus, where it is removed by PSME4, promoting cardiac commitment. The failure of YAP1 to translocate or be eliminated from the nucleus results in the MSCs' inability to undergo cardiac commitment.

• Journal of Life Science
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• v.17 no.8 s.88
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• pp.1063-1067
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• 2007

The Bcl-2 family proteins play critical roles in regulation of apoptosis, and the balanced interaction of pro- and anti-death members is a key factor in determining the cell fate. Noxa, a BH3-only Bcl-2-family member, has been originally identified as a target gene of p53. To understand the mechanism by which human Noxa (hNoxa) regulates the cell death, we screened the hNoxa binding partner using the yeast two hybrid screening and found that anti-death protein Mcl-1 binds to hNoxa. The binding of hNoxa to Mcl-1 was confirmed by immunoprecipitation in human colon cancer cell line HCT 116 cells. Mcl-1 significantly inhibited the hNoxa-induced cell death in HCT 116 cells. During the cell death induced by hNoxa, Mcl-1 protein was degraded. Its degradation was inhibited by z-VAD-fmk, a pancaspase inhibitor, suggesting caspase is responsible for Mcl-1 degradation in response to hNoxa. Together, the results indicate that hNoxa binds to Mcl-1 that is degraded by cas-pases during hNoxa-induced cell death.

• Journal of Soil and Groundwater Environment
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• v.12 no.5
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• pp.115-123
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• 2007

Immobilization of contaminants in subsurface environment is one of the major processes that determine their fate. Especially, immobilization by oxidative-coupling reactions, which is irreversible in the bio-chemical reactions and results in a significant reduction of toxicity, can be successfully applied for the remediation of contaminated soil and groundwater more effectively than conventional degradation. As a catalyst of this oxidative-coupling reaction, manganese oxide has many advantages in practical aspects as compared to microorganisms or oxidoreductive enzymes extracted from microorganisms, fungi, or plants. This paper is to present recent research achievements on the treatment mechanisms of various organic contaminants by manganese oxide. Especially, treatment methods of non-reactive organic compounds to Mn oxide are the main focus; i.e., application of reaction mediator, PAHs treatment method, combination with an appropriate pretreatment such as reduction using $Fe^0$, which suggests the potential of a wide range of engineering application. Concerning the natural carbon cycle processes, immobilization and stabilization by oxidative coupling reaction can be effectively applied as a environmentally-friend remediation method especially for aromatic contaminants which possess a high resistance to degradation.