• The Korean Journal of Physiology and Pharmacology
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• v.23 no.3
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• pp.171-179
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• 2019

Pituitary tumors are usually benign but can occasionally exhibit hormonal and proliferative behaviors. Dysregulation of the G1/S restriction point largely contributes to the over-proliferation of pituitary tumor cells. F-box protein S-phase kinase-interacting protein-2 (SKP2) reportedly targets and inhibits the expression of $p27^{Kip1}$, a well-known negative regulator of G1 cell cycle progression. In this study, SKP2 expression was found to be upregulated while $p27^{Kip1}$ expression was determined to be downregulated in rat and human pituitary tumor cells. Furthermore, SKP2 knockdown induced upregulation of $p27^{Kip1}$ and cell growth inhibition in rat and human pituitary tumor cells, while SKP2overexpression elicited opposite effects on $p27^{Kip1}$ expression and cell growth. The expression of microRNA-186 (miR-186) was reported to be reduced in pituitary tumors. Online tools predicted SKP2 to be a direct downstream target of miR-186, which was further confirmed by luciferase reporter gene assays. Moreover, miR-186 could modulate the cell proliferation and $p27^{Kip1}$-mediated cell cycle alternation of rat and human pituitary tumor cells through SKP2. As further confirmation of these findings, miR-186 and $p27^{Kip1}$ expression were downregulated, while SKP2 expression was upregulated in human pituitary tumor tissue samples; thus, SKP2 expression negatively correlated with miR-186 and $p27^{Kip1}$ expression. In contrast, miR-186 expression positively associated with $p27^{Kip1}$ expression. Taken together, we discovered a novel mechanism by which miR-186/SKP2 axis modulates pituitary tumor cell proliferation through $p27^{Kip1}$-mediated cell cycle alternation.

• Journal of Microbiology
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• v.39 no.4
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• pp.286-292
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• 2001

During mitosis. the proper segregation of duplicated chromosomes is corrdinated by a spindle check-point. The bifurcated spindle checkpoint blocks cell cycle progression at metaphase by monitoring unattached kinetochores and inhibits mitotic exit in response to the misorientation of the mitotic spin- dle Ibd1p/Bfa1p is a spindle checkpoint regulator of budding yeast in the Bub2p checkpoint pathway for mitotic exit and its disruption abolishes mitotic arrest when proper organization of the mitotic spin-dls inhibited. Ibd1p/Bfa1p localizes to the spindle pole body, a microtublue-organizing center in yeast, and its overexpression arrests the cell cycle in 80% of cells with an enlarged budy at mitosis and in 20 % of cells with multiple buds. In this study, we found that the C-terminus of Ibd1p/Bfa1p phys-ically interacts with Skp1p, a key component of SCF (Skp1/cullin/F-box) complex for ubiquition-medi-ated proteolysis of cel cycle regulatores as well as an evolutionally conserved kinetochore protein for cell cycle progression. A putative F-box motif was found in the C-terminus of Ibd1p/Bfa1p and its function was investigated by making mutants of conserved residues in the motif. These Ibd1p/Bfa1p mutants of a putative F-box interacted with SKp1p in vitro by two-hybrid assays as wild type Ibd1p/Bfa1p. Also these Ibd1p/Bfa1p utants displayed the overexpression phenotypes of wild type Ibd1p, when over-expressed under inducible promoters . These results suggest that a putative F-box motif of Ibd1p/Bfa1p is not essential for the interaction with SKp1p and its function in mitotic exit and cytokinesis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5807-5815
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• 2015

Background: Ovarian cancer is the most common gynecological malignancy and constitutes the fifth leading cause of female cancer death. Some biological parameters have prognostic roles in patients with advanced ovarian cancer and their expression may contribute to tumor progression. The aim of this study was to investigate the potential prognostic value of SKP2, genes P27Kip1, K-ras, c-Myc, COX2 and HER2 genes expression in ovarian cancer. Materials and Methods: This study was performed on two hundred formalin fixed paraffin embedded ovarian cancer and normal adjacent tissues (NAT). Gene expression levels were assessed using real time PCR and Western blotting. Results: Elevated expression levels of SKP2, K-ras, c-Myc, HER2 and COX2 genes were observed in 61.5% (123/200), 92.5% (185/200), 74% (148/200), 96 % (192/200), 90% (180/200) and 78.5% (157/200) of cancer tissues, respectively. High expression of SKP2 and down-regulation of P27 was associated with advanced stages of cancer. Conclusions: The association between high expression of c-Myc and SKP2 with low expression of P27 suggested that the Skp2-P27 pathway may play an important role in ovarian carcinogenesis. Reduced expression of P27 is associated with advanced stage of cancer and can be used as a biological marker in clinical routine assessment and management of women with advanced ovarian cancer.

• Economic and Environmental Geology
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• v.39 no.1 s.176
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• pp.83-93
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• 2006

The Kita-Yamato Trough is characterized by a SW-NE trending narrow graben between the Yamato Bank and the Kita-Yamato Bank in the central East Sea/Japan Sea (ES/JS). Core 20EEZ-1 was obtained in the flat summit of a small ridge from the southwest Kita-Yamato Trough. The sedimentation was mainly controlled by the supply of hemipelgic sediments and substantial tephras from explosive volcanic eruptions of the Quaternary volcanoes. The aim of this study is to reconstruct the tephrostratigraphy from the marine sediments collected from the Kita-Yamato Trough and to provide the atmosphere and ocean conditions during the explosive volcanic eruptions. According to the detailed tephrostratigraphy and lithofacies records, the core sediments were deposited during the last marine isotope stage (MIS) 7. The core consists of four lithofacies, idetified as, oxidized mud (OM), crudely laminated mud (CLM) and bioturbated mud (BM), interbedded with coarse-grained tephra (TP). The major element geochemistry and stratigraphic positions of seven tephra layers suggest that they originated from the Aira caldera in Kyushu area among the Japanese islands (AT tephra; 29.24 ka), unknown submarine volcano in the south Korea Plateau (SKP-I; MIS 3, SKP-II; MIS 4, SKP-IV; boundary between MIS 6 and MIS 5e, SKP-V; MIS 6, respectively), and the Baegdusan volcano in the Korean Peninsula (B-KY1; ca. 130 ka, B-KY2; ca. 196 ka). The absence of tephras originated trom Ulleung Island in core 20EEZ-l suggest that the tephras had not been transported into the Kita-Yamato Trough by atmosphere conditions during the eruptions. On the other hand, the B-KYI and the B-KY2 tephras derived from the Baegdusan volcano were founded in the Kita-Yamato Trough by a presence of prevailing westerly winds during the eruptions. Furthermore, the SKP tephras were characterized by the transport across the air-water interface, causing quickly thrust of raising eruption plumes from subaqueous explosive eruptions. Surface currents may play an important role in controlling the distribution patterns of the SKP tephras to distal areas. The tephrostratigraphic study in the Kita-Yamato Trough provides the important chronostratigraphic marker horizons and the detailed atmosphere and ocean conditions during the explosive eruptions.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3805-3810
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• 2015

Arsenic trioxide (ATO) has been found to exert anti-cancer activity in various human malignancies. However, the molecular mechanisms by which ATO inhibits tumorigenesis are not fully elucidated. In the current study, we explored the molecular basis of ATO-mediated tumor growth inhibition in pancreatic cancer cells. We used multiple approaches such as MTT assay, wound healing assay, Transwell invasion assay, annexin V-FITC, cell cycle analysis, RT-PCR and Western blotting to achieve our goal. We found that ATO treatment effectively caused cell growth inhibition, suppressed clonogenic potential and induced G2-M cell cycle arrest and apoptosis in pancreatic cancer cells. Moreover, we observed a significant down-regulation of Skp2 after treatment with ATO. Furthermore, we revealed that ATO regulated Skp2 downstream genes such as FOXO1 and p53. These findings demonstrate that inhibition of Skp2 could be a novel strategy for the treatment of pancreatic cancer by ATO.

• Journal of Korea Water Resources Association
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• v.48 no.9
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• pp.719-728
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• 2015

In this study, urban runoff analyses were performed using high resolution Quantitative Precipitation Estimation (QPE), and variation of rainfall and runoff were analyzed to evaluate QPE data for urban runoff analysis. The five drainage districts (Seocho3, 4, 5, Yeoksam and Nonhyun) around Gangnam station were chosen as study area, the area is $7.4km^2$. Rainfall data from KMA AWS (34 stations), SKP AWS (156 stations) and Gwanduk radar were used for QPEs in Seoul area. Four types of QPE(QPE1: KMA AWS, QPE2: KMA+ SKP AWS, QPE3: Gwangduk radar, QPE4: QPE2+QPE3) of 6 events in July 2013 were generated by using Krigging and conditional merging. The temporal and spatial resolution of QPEs are 10 minutes and 250 m, respectively. The complex pipe network were treated as 773 manholes, 772 sub-drainage districts and 1,059 pipelines for urban runoff analysis as input data. QPE2 and QPE4 show spatial variation of rainfall by sub-drainage districts as 1.9 times bigger than QPE1. The peak runoff of QPE2 and QPE4 also show spatial variation as 6 times bigger than Gangnam and Seocho AWS. Thus, the spatial variation of rainfall and runoff could exist in small area such as this study area, and using high-resolution rainfall data is desirable for accurate urban runoff analysis.

• Ocean and Polar Research
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• v.29 no.1
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• pp.9-31
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• 2007

Most seismic sea waves in the East Sea originate from earthquakes occurring near the Japanese west coast. While the waves propagate in the East Sea, they are deformed by refraction, diffraction and scattering. Though the Boussinesq equation is most applicable for such wave phenomena, it was not used in numerical modelling of seismic sea waves in the East Sea. To examine characteristics of seismic sea waves in the East Sea, numerical models based on the Boussinesq equation are established and used to simulate recent tsunamis. By considering Ursell parameter and Kajiura parameter, it is proved that Boussinesq equation is a proper equation for seismic sea waves in the East Sea. Two models based on the Boussinesq equation and linear wave equation are executed with the same initial conditions and grid size ($1min{\times}1min$), and the results are compared in various respects. The Boussinesq equation model produced better results than the linear model in respect to wave propagation and concentration of wave energy. It is also certified that the Boussinesq equation model can be used for operational purpose if it is optimized. Another Boussinesq equation model whose grid size is $40sec{\times}30sec$ is set up to simulate the 1983 and 1993 tsunamis. As the result of simulation, new propagation charts of 2 seismic sea waves focused on the Korean east coast are proposed. Even though the 1983 and 1993 tsunamis started at different areas, the propagation paths near the Korean east coast are similar and they can be distinguished into 4 paths. Among these, total energy and propagating time of the waves passing over North Korea Plateau(NKP) and South Korea Plateau(SKP) determine wave height at the Korean east coast. In case of the 1993 tsunami, the wave passing over NKP has more energy than the wave over SKP. In case of the 1983 tsunami, the huge energy of the wave passing over SKP brought about great maximum wave heights at Mukho and Imwon. The Boussinesq equation model established in this study is more useful for simulation of seismic sea waves near the Korean east coast than it is the Japanese coast. To improve understanding of seismic sea waves in shallow water, a coastal area model based on the Boussinesq equation is also required.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.677-682
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• 2014

Resveratrol has been examined in several model systems for potential effects against cancer. Adenosine monophosphate-activated protein kinase (AMPK) is reported to suppress proliferation in most eukaryocyte cells. Whether resveratrol via AMPK inhibits proliferation of oesophageal adenocarcinoma cells (OAC) is unknown. The aim of this study was to determine the roles of AMPK in the protective effects of resveratrol in OAC proliferation and to elucidate the underlying mechanisms. Treatment of cultured OAC derived from human subjects or cell lines with resveratrol resulted in decreased cell proliferation. Further, inhibition of AMPK by pharmacological reagent or genetical approach abolished resveratrol-suppressed OAC proliferation, reduced the level of $p27^{Kip1}$, a cyclin-dependent kinase inhibitor, and increased the levels of S-phase kinase-associated protein 2 (Skp2) of $p27^{Kip1}$-E3 ubiquitin ligase and 26S proteasome activity reduced by resveratrol. Furthermore, gene silencing of $p27^{Kip1}$ reversed resveratrol-suppressed OAC proliferation. In conclusion, these findings indicate that resveratrol inhibits Skp2-mediated ubiquitylation and 26S proteasome-dependent degradation of $p27^{Kip1}$ via AMPK activation to suppress OAC proliferation.

• Proceedings of the Korea Water Resources Association Conference
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• 2015.05a
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• pp.640-640
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• 2015

2010년과 2011년 서울에서 발생한 집중호우와 2014년 부산에서 발생한 집중호우의 발생으로 막대한 재산상의 피해와 사상자를 냈다. 2010년 9월 21일에 발생한 집중호우는 1908년 관측시작이래 가장 많은 비가 내린 것으로 기록되었으며 주거지 4,727호, 상가 1,164호, 공장 126동 등이 침수되고 13시를 기준으로 강서지점의 경우 시간당 98.5mm의 기록적인 강우를 기록하였으나, 관악지점은 5.5mm에 그쳐 두 지점간의 시간당 강우량의 편차가 약 200배 가까이 차이가 나는 것으로 나타났다. 이와 같이 최근 도시지역에서 국지성 집중호우가 증가하고 있으며 지역별 강우 편차가 크고 이에 따라 침수피해발생 여부도 지역에 따라 달라진다. 강수의 공간적 분포와 그로 인한 침수해석은 도시돌발홍수 예경보 시스템에 있어 무엇보다도 중요하다. 본 연구의 목적은 도시지역 돌발홍수 예경보 시스템 구축을 위한 정량적 강수추정 QPE(Quantitative Precipitation Estimation)기법에 따른 수리 수문학적 영향을 평가하는 것이다. 정량적 강수추정을 위해 AWS, SKP, 레이더 자료를 활용하여 250m의 해상도를 가지도록 크리깅을 적용하였다: QPE 1은 34개의 AWS의 지점우량을 지구통계학적 기법 중의 하나인 크리깅을 이용하여 산정한 기법, QPE 2는 AWS와 156개의 SKP의 강우데이터를 크리깅을 이용하여 산정한 기법, QPE 3는 광덕산 레이더를 이용한 기법, QPE 4는 AWS, SKP, 광덕산 레이더 자료를 조건부 합성한 기법이다. 월류량을 산정하기 위해 도시유출해석모형인 SWMM을 강남역 일대를 대상으로 구축하고 우수관로 시스템으로 유입되지 못한 노면류(Surface flow)를 함께 고려하였다. 침수해석을 위해서는 DHM모델을 적용하였으며 2013년 7월 기간에 발생한 호우에 대하여 분석을 수행하였다. 비교수행을 위해서 인접한 서초 AWS와 강남 AWS의 지점강우량도 함께 고려하였으며 모의결과를 국가 재난관리 정보 시스템(NMDS)에 침수피해가 확인된 가옥 및 빌딩 정보와 일치여부를 적합도로 산정하였다. 산정된 적합도를 통하여 정량적 강수추정기법에 따른 수리?수문학적 영향을 평가하였다. 실제 침수흔적정보와 비교 결과, QPE 2와 QPE4가 가장 적합도가 높았으며 이에 따라 고밀도의 관측망의 구성이 도시지역 침수해석결과에도 적합할 것으로 판단된다.

• Molecules and Cells
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• v.42 no.12
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• pp.840-849
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• 2019

The spatiotemporal mitotic processes are controlled qualitatively by phosphorylation and qualitatively by ubiquitination. Although the SKP1-CUL1-F-box protein (SCF) complex and the anaphase-promoting complex/cyclosome (APC/C) mainly mediate ubiquitin-dependent proteolysis of mitotic regulators, the E3 ligase for a large portion of mitotic proteins has yet to be identified. Here, we report c-Cbl as an E3 ligase that degrades DDA3, a protein involved in spindle dynamics. Depletion of c-Cbl led to increased DDA3 protein levels, resulting in increased recruitment of Kif2a to the mitotic spindle, a concomitant reduction in spindle formation, and chromosome alignment defects. Furthermore, c-Cbl depletion induced centrosome over-duplication and centriole amplification. Therefore, we concluded that c-Cbl controls spindle dynamics and centriole duplication through its E3 ligase activity against DDA3.