• Journal of Life Science
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• v.33 no.6
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• pp.523-529
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• 2023

Ubiquitination is a post-translational modification that is involved in the quality control of proteins and responsible for modulating a variety of cellular physiological processes. Protein ubiquitination and deubiquitination are reversible processes that regulate the stability of target substrates. The ubiquitin proteasome system (UPS) helps regulate tumor-promoting processes, such as DNA repair, cell cycle, apoptosis, metastasis, and angiogenesis. The UPS comprises a combination of ubiquitin, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin-ligase enzymes (E3), which complete the degradation of target proteins. Ubiquitin-conjugating enzymes (UBE2s) play an inter-mediate role in the UPS process by moving activated ubiquitin to target proteins through E3 ligases. UBE2s consist of 40 members and are classified according to conserved catalytic ubiquitin-conjugating (UBC) domain-flanking extensions in humans. Since UBE2s have specificity to substrates like E3 ligase, the significance of UBE2 has been accentuated in tumorigenesis. The dysregulation of multiple E2 enzymes and their critical roles in modulating oncogenic signaling pathways have been reported in several types of cancer. The elevation of UBE2 expression is correlated with a worse prognosis in cancer patients. In this review, we summarize the basic functions and regulatory mechanisms of UBE2s and suggest the possibility of their use as therapeutic targets for cancer.

• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1206-1212
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• 2023

The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N⁶-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1265-1276
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• 1998

Background : Nitric oxide(NO) is an endogenously produced free radical that plays an important role in regulating vascular tone, inhibition of platelet aggregation and white blood cell adhesion to endothelial cells, and host defense against infection. The highly reactive nature of NO with oxygen radicals suggests that it may either promote or reduce oxidant-induced cell injury in several biological pathways. Oxidant injury and interactions between pulmonary vascular endothelium and leukocytes are important in the pathogenesis of acute lung injury, including acute respiratory distress syndrome(ARDS). In ARDS, therapeutic administration of NO is a clinical condition providing exogenous NO in oxidant-induced endothelial injury. The role of exogenous NO from NO donor or the suppression of endogenous NO production was evaluated in oxidant-induced endothelial injury. Method : The oxidant injury in cultured rat lung microvascular endothelial cells(RLMVC) was induced by hydrogen peroxide generated from glucose oxidase(GO). Cell injury was evaluated by $^{51}$chromium($^{51}Cr$) release technique. NO donor, such as S-nitroso-N-acetylpenicillamine(SNAP) or sodium nitroprusside(SNP), was added to the endothelial cells as a source of exogenous NO. Endogenous production of NO was suppressed with N-monomethyl-L-arginine(L-NMMA) which is an NO synthase inhibitor. L-NMMA was also used in increased endogenous NO production induced by combined stimulation with interferon-$\gamma$(INF-$\gamma$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and lipopolysaccharide(LPS). NO generation from NO donor or from the endothelial cells was evaluated by measuring nitrite concentration. Result : $^{51}Cr$ release was $8.7{\pm}0.5%$ in GO 5 mU/ml, $14.4{\pm}2.9%$ in GO 10 mU/ml, $32.3{\pm}2.9%$ in GO 15 mU/ml, $55.5{\pm}0.3%$ in GO 20 mU/ml and $67.8{\pm}0.9%$ in GO 30 mU/ml ; it was significantly increased in GO 15 mU/ml or higher concentrations when compared with $9.6{\pm}0.7%$ in control(p < 0.05; n=6). L-NMMA(0.5 mM) did not affect the $^{51}Cr$ release by GO. Nitrite concentration was increased to $3.9{\pm}0.3\;{\mu}M$ in culture media of RLMVC treated with INF-$\gamma$ (500 U/ml), TNF-$\alpha$(150 U/ml) and LPS($1\;{\mu}g/ml$) for 24 hours ; it was significantly suppressed by the addition of L-NMMA. The presence of L-NMMA did not affect $^{51}Cr$ release induced by GO in RLMVC pretreated with INF-$\gamma$, TNF-$\alpha$ and LPS. The increase of $^{51}Cr$ release with GO(20 mU/ml) was prevented completely by adding 100 ${\mu}M$ SNAP. But the add of SNP, potassium ferrocyanate or potassium ferricyanate did not protect the oxidant injury. Nitrite accumulation was $23{\pm}1.0\;{\mu}M$ from 100 ${\mu}M$ SNAP at 4 hours in phenol red free Hanks' balanced salt solution. But nitrite was not detectable from SNP upto 1 mM The presence of SNAP did not affect the time dependent generation of hydrogen peroxide by GO in phenol red free Hanks' balanced salt solution. Conclusion : Hydrogen peroxide generated by GO causes oxidant injury in RLMVC. Exogenous NO from NO donor prevents oxidant injury, and the protective effect may be related to the ability to release NO. These results suggest that the exogenous NO may be protective on oxidant injury to the endothelium.

• Journal of Plant Biotechnology
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• v.33 no.1
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• pp.1-9
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• 2006

Peroxiredoxins (Prxs) are ubiquitously distributed and play important functions in diverse cellular signaling systems. The proteins are largely classified into three groups, such as typical 2-Cys Prx, atypical 2-Cys Prx, and 1-Cys Prx, that are distinguished by their catalytic mechanisms and number of Cys residues. From the three classes of Prxs, the typical 2-Cys Prx containing the two-conserved Cys residues at its N-terminus and C-terminus catalyzes $H_2O_2$ with the use of thioredoxin (Trx) as an electron donor. During the catalytic cycle, the N-terminal Cys residue undergoes a peroxide-dependent oxidation to sulfenic acid, which can be further oxidized to sulfinic acid at the presence of high concentrations of $H_2O_2$ and a Trx system containing Trx, Trx reductase, and NADPH. The sulfinic acid form of 2-Cys Prx is reduced by the action of sulfiredoxin which requires ATP as an energy source. Under the strong oxidative or heat shock stress conditions, 2-Cys Prx in eukaryotes rapidly switches its protein structure from low-molecular-weight species to high-molecular-weight protein structures. In accordance with its structural changes, the protein concomitantly triggers functional switching from a peroxidase to a molecular chaperone, which can protect its substrate denaturation from external stress. In addition to its N-terminal active site, the C-terminal domain including 'YF-motif' of 2-Cys Prx plays a critical role in the structural changes. Therefore, the C-terminal truncated 2-Cys Prxs are not able to regulate their protein structures and highly resistant to $H_2O_2$-dependent hyperoxidation, suggesting that the reaction is guided by the peroxidatic Cys residue. Based on the results, it may be concluded that the peroxidatic Cys of 2-Cys Prx acts as an '$H_2O_2$-sensor' in the cells. The oxidative stress-dependent regulation of 2-Cys Prx provides a means of defense systems in cells to adapt stress conditions by activating intracellular defense signaling pathways. Particularly, 2-Cys Prxs in plants are localized in chloroplasts with a dynamic protein structure. The protein undergoes conformational changes again oxidative stress. Depending on a redox-potential of the chloroplasts, the plant 2-Cys Prx forms super-molecular weight protein structures, which attach to the thylakoid membranes in a reversible manner.

• Journal of the Korean Society for Marine Environment & Energy
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• v.19 no.4
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• pp.322-331
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• 2016

Oil budget calculator identifies the removal pathways of spilled oil by both natural and response methods, and estimates the remaining oil required response activities. A oil budget calculator was newly developed as a response tool for Deepwater Horizon oil spill incident in Gulf of Mexico in 2010 to inform clean up decisions for Incident Comment System, which was also successfully utilized to media and general public promotion of oil spill response activities. This study analyzed the theoretical background of the oil budget calculator and explored its future application to Korea. The oil budge calculation of four catastrophic marine pollution incidents indicates that 3~8% of spilled oil was removed mechanically by skimmers, 1~5% by in-situ burning, 4.8~16% by chemical dispersion due to dispersant operation, and 37~56% by weathering processes such as evaporation, dissolution, and natural dispersion. The results show that in-situ burning and chemical dispersion effectively remove spilled oil more than the mechanical removal by skimming, and natural weathering processes are also very effective to remove spilled oil. To apply the oil budget calculator in Korea, its parameters need to be optimized in response to the seasonal characteristics of marine environment, the characteristics of spilled oil and response technologies. A new algorithm also needs to be developed to estimate the oil budget due to shoreline cleanup activities. An oil budget calculator optimized in Korea can play a critical role in informing decisions for oil spill response activities and communicating spill prevention and response activities with the media and general public.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3395-3402
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• 2015

Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

• Proceedings of the Korean Vacuum Society Conference
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• 2012.02a
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• pp.100-101
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• 2012

The plasma damage free and room temperature processedthin film deposition technology is essential for realization of various next generation organic microelectronic devices such as flexible AMOLED display, flexible OLED lighting, and organic photovoltaic cells because characteristics of fragile organic materials in the plasma process and low glass transition temperatures (Tg) of polymer substrate. In case of directly deposition of metal oxide thin films (including transparent conductive oxide (TCO) and amorphous oxide semiconductor (AOS)) on the organic layers, plasma damages against to the organic materials is fatal. This damage is believed to be originated mainly from high energy energetic particles during the sputtering process such as negative oxygen ions, reflected neutrals by reflection of plasma background gas at the target surface, sputtered atoms, bulk plasma ions, and secondary electrons. To solve this problem, we developed the NBAS (Neutral Beam Assisted Sputtering) process as a plasma damage free and room temperature processed sputtering technology. As a result, electro-optical properties of NBAS processed ITO thin film showed resistivity of $4.0{\times}10^{-4}{\Omega}{\cdot}m$ and high transmittance (>90% at 550 nm) with nano- crystalline structure at room temperature process. Furthermore, in the experiment result of directly deposition of TCO top anode on the inverted structure OLED cell, it is verified that NBAS TCO deposition process does not damages to the underlying organic layers. In case of deposition of transparent conductive oxide (TCO) thin film on the plastic polymer substrate, the room temperature processed sputtering coating of high quality TCO thin film is required. During the sputtering process with higher density plasma, the energetic particles contribute self supplying of activation & crystallization energy without any additional heating and post-annealing and forminga high quality TCO thin film. However, negative oxygen ions which generated from sputteringtarget surface by electron attachment are accelerated to high energy by induced cathode self-bias. Thus the high energy negative oxygen ions can lead to critical physical bombardment damages to forming oxide thin film and this effect does not recover in room temperature process without post thermal annealing. To salve the inherent limitation of plasma sputtering, we have been developed the Magnetic Field Shielded Sputtering (MFSS) process as the high quality oxide thin film deposition process at room temperature. The MFSS process is effectively eliminate or suppress the negative oxygen ions bombardment damage by the plasma limiter which composed permanent magnet array. As a result, electro-optical properties of MFSS processed ITO thin film (resistivity $3.9{\times}10^{-4}{\Omega}{\cdot}cm$, transmittance 95% at 550 nm) have approachedthose of a high temperature DC magnetron sputtering (DMS) ITO thin film were. Also, AOS (a-IGZO) TFTs fabricated by MFSS process without higher temperature post annealing showed very comparable electrical performance with those by DMS process with $400^{\circ}C$ post annealing. They are important to note that the bombardment of a negative oxygen ion which is accelerated by dc self-bias during rf sputtering could degrade the electrical performance of ITO electrodes and a-IGZO TFTs. Finally, we found that reduction of damage from the high energy negative oxygen ions bombardment drives improvement of crystalline structure in the ITO thin film and suppression of the sub-gab states in a-IGZO semiconductor thin film. For realization of organic flexible electronic devices based on plastic substrates, gas barrier coatings are required to prevent the permeation of water and oxygen because organic materials are highly susceptible to water and oxygen. In particular, high efficiency flexible AMOLEDs needs an extremely low water vapor transition rate (WVTR) of $1{\times}10^{-6}gm^{-2}day^{-1}$. The key factor in high quality inorganic gas barrier formation for achieving the very low WVTR required (under ${\sim}10^{-6}gm^{-2}day^{-1}$) is the suppression of nano-sized defect sites and gas diffusion pathways among the grain boundaries. For formation of high quality single inorganic gas barrier layer, we developed high density nano-structured Al2O3 single gas barrier layer usinga NBAS process. The NBAS process can continuously change crystalline structures from an amorphous phase to a nano- crystalline phase with various grain sizes in a single inorganic thin film. As a result, the water vapor transmission rates (WVTR) of the NBAS processed $Al_2O_3$ gas barrier film have improved order of magnitude compared with that of conventional $Al_2O_3$ layers made by the RF magnetron sputteringprocess under the same sputtering conditions; the WVTR of the NBAS processed $Al_2O_3$ gas barrier film was about $5{\times}10^{-6}g/m^2/day$ by just single layer.

• Journal of Korean Society of Environmental Engineers
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• v.27 no.7
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• pp.746-752
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• 2005

In this study, the effect of reaction parameters including reaction temperature, time, and pressure on sludge degradation and conversion to intermediates such as organic acids were investigated at low critical wet air oxidation(LC-WAO) conditions. Degradation pathways and a modified kinetic model in LC-WAO were proposed and the kinetics model predictions were compared with experimental data under various conditions. Results in the batch experiments showed that reaction temperature directly affected the thermal hydrolysis reaction rather than oxidation reaction. The efficiencies of sludge degradation and organic acid formation increased with the increase of the reaction temperature and time. The removal of SS at $180^{\circ}C$, $200^{\circ}C$, $220^{\circ}C$ and $240^{\circ}C$ of reaction temperatures and 10 min of reaction time were 52.6%, 68.3%, 72.6%, and 74.4%, respectively, indicating that most organic suspended solids were liquified at early stage of reaction. At $180^{\circ}C$, $200^{\circ}C$, $220^{\circ}C$ and $240^{\circ}C$ of reaction temperatures and 40 min of reaction time, the amounts of organic acids formed from 1 g of sludge were 93.5 mg/g SS, 116.4 mg/g SS, 113.6 mg/g SS, and 123.8 mg/g SS, respectively, and the amounts of acetic acid from 1 g of sludge were 24.5 mg/g SS, 65.5 mg/g SS, 88.1 mg/g SS, and 121.5 mg/g SS, respectively. This suggested that the formation of sludge to organic acids as well as the conversion of organic acids to acetic acid increased with reaction temperature. Based on the experimental results, a modified kinetic model was suggested for the liquefaction reaction of sludge and the formation of organic acids. The kinetic model predicted an increase in kinetic parameters $k_1$ (liquefaction of organic compounds), $k_2$ (formation of organic acids to intermediate), $k_3$ (final degradation of intermediate), and $k_4$ (final degradation of organic acids) with reaction temperature. This indicated that the liquefaction of organic solid materials and the formation of organic acids increase according to reaction temperature. The calculated activation energy for reaction kinetic constants were 20.7 kJ/mol, 12.3 kJ/mol, 28.4 kJ/mol, and 54.4 kJ/mol, respectively, leading to a conclusion that not thermal hydrolysis but oxidation reaction is the rate-limiting step.

• Korea journal of population studies
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• v.20 no.2
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• pp.181-198
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• 1997

Going beyond the previous formulations of development theories, the present paper explores the effects other than political economy on quality of life in a rapidly developing country. The major analysis takes up the historical trend and nature of the developmental transformation that is partially a consequences of state structures and partially autonomous form it in South Korea. Also, it diagnoses developmental pathways for the future track by constructing a baseline model for state transition on the basis of power game between the state and civil society in the country. The results of the historical analysis show that civil society has been transformed in the course of confrontations and interactions between the state and nationalist social movement. The distinction between developmental(or bureaucratic authoritarian) and democratic state is presented to show that these are two qualitatively different aspects of state of state power, requiring separate analytical treatment. Furthermore, the state-centric approach which emphasizes the active role of the state at the sacrifice of societal fabric-constraining social conditions for quality of life - appears to be modified. On the contrary, the impact of civil society is transmitted both directly and indirectly via labor and ecological movement for quality of life, which is critical to the formation of the welfare state in the country. The prospect for sustainable development in Korea lies in providng and expanding quality of life in terms of the financial feasibility of the state through the public-private cooperation, and abstaining from drastic and radical commitment to welfare services as is the case with the European declines in welfare state, Further studies are needed to examine the interrelationships in different historical and cultural settings of developing counties to estimate a theory of quality of life and social justice.

• Journal of Life Science
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• v.24 no.6
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• pp.664-670
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• 2014

In the present study, we investigate the role of V. vulnificus in promoting the inflammation of mouse ileal ephitelium and its related signaling pathways. ICR mice were infected orally with V. vulnificus ($1{\times}10^9CFU$) for 16 h as a representative model of food-borne infection. To find the major portal of entry of V. vulnificus in mouse intestine, we have measured the levels of bacterial colonization in small intestine, colon, spleen, and liver. V. vulnificus appeared to colonize in intestine and colon in the order of ileum >> jejunum> colon, but lack in the duodenum, spleen, and liver. V. vulnificus in ileum caused severe necrotizing enteritis and showed shortened villi heights accompanied by an expanded width and inflammation, compared with the control mice. V. vulnificus induced ileal epithelium inflammation by activating phosphorylation of PKC and membrane translocation of $PKC{\alpha}$. V. vulnificus induced the phosphorylation of ERK and JNK, but did not affect p38 MAPK phosphorylation. Notably, V. vulnificus stimulated the I-${\kappa}B$-dependent phosphorylation of NF-${\kappa}B$ in mouse ileal epithelium. Finally, the ileal infection of V. vulnificus resulted in a significant increase in expression of proinflammatory cytokines and Toll-like receptors, respectively, compared to the control. Collectively, our results indicate that V. vulnificus induces ileal epithelium inflammation by increasing NF-${\kappa}B$ phosphorylation via activation of PKC, ERK, and JNK, which is critical for host defense mechanism in food-borne infection by V. vulnificus.