• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.345-350
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• 1998

The adverse effects of ethanol on cell proliferation have been described for a variety of tissues and cells. In the present study, we investigated whether chronic ethanol intoxication impairs the cell proliferation and DNA synthesis induced by oncogenic $H-ras^{V12}$ - and $v-K-ras^{V12}$-transformed cells. Ethanol treatment inhibited the cell proliferation and the DNA synthesis of control parental fibroblasts in a time- and dose-dependent manner. In contrast, ethanol did not suppress the proliferation of either oncogenic $H-ras^{V12}$ - or $v-K-ras^{V12}$ -transformed fibroblasts. Microinjection of oncogenic $H-Ras^{V12}$ protein induces DNA synthesis and ethanol treatment did not interfere with the DNA synthesis. The antiproliferative toxicity of ethanol was rescued by antioxidants, such as N-acetylcysteine and 4-methlpyrazole. These results indicate that the antiproliferative action site of ethanol toxicity lies upstream or is independent of Ras and ethanol exerts its toxicity through a free radical formation.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.157-157
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• 2001

• BMB Reports
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• v.50 no.7
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• pp.355-360
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• 2017

Mutations in Ras GTPase are among the most common genetic alterations in human cancers. Despite extensive research investigating Ras proteins, their functions still remain a challenge over a long period of time. The currently available data suggests that solving the outstanding issues regarding Ras could lead to development of effective drugs that could have a significant impact on cancer treatment. Developing a better understanding of their biochemical properties or modes of action, along with improvements in their pharmacologic profiles, clinical design and scheduling will enable the development of more effective therapies.

• Applied Microscopy
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• v.35 no.3
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• pp.121-128
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• 2005

It has been known that ras signaling transduction leads to cell proliferation and migration including various adaptor molecules. Dynamin protein has been implicated in the formation of nascent vesicles in both the endocytic and secretory pathways. Dynamin was classified into three isoforms: dynamin I is only expressed in neuronal tissue, dynamin II is expressed ubiquitously in all tissue but that of dynamin III is confined to testis. We have reported in previous study that Grb2, binding to ras, was associated with dynamin II in NIH3T3 cells. Therefore we have tried to identify the relative expression of dynamin II according to overexpressed ras protein in ras oncogene transfected cells (NIH3T3 (ras)). For the detection of differential expression of dynamin II, we have used immunofluorescent staining and western blot methods in NIH3T3 and NIH3T3 (ras) cells. Next we have described the morphological differences between NIH3T3 and NIH3T3 (ras) cells using SEM and TEM. From these experiments dynamin II was highly expressed in NIH3T3 (ras) cells. NIH3T3 cells was transformed to more spindle shape with many cell process by transfection of ras oncogene. Moreover dynamin II was more concentrated in endocytotic membrane of the NIH3T3 (ras) cells compared to that of NIH3T3 cells. The present results suggested that dynamin II may involve the intermediate messenger in Ras signaling transduction pathway.

• Journal of Powder Materials
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• v.27 no.6
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• pp.458-463
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• 2020

Hispidin is a secondary metabolite found in numerous medicinal mushrooms that has attracted significant attention, owing to its distinct biological effects, including antioxidant, anti-inflammatory, antitumor, and cytoprotective properties. Experiments are being carried out to study the interaction of detonation nanodiamonds (DNDs) with synthetic and natural hispidin sourced from extracts of Pholiota sp. fungus. The bioluminescence method is used to determine the adsorption/desorption properties of DNDs toward hispidin. It is found that hispidin forms strong conjugates with DNDs, and the use of various eluents does not result in a significant release of the adsorbed hispidin molecules. DND-bovine serum albumin (BSA) complex, where DNDs serve as a carrier for the protein and the latter acts as a hispidin sorbent, has been developed and applied in hispidin adsorption/desorption tests. The results support the use of the DNDs as a carrier for hispidin in medical applications. They also advocate the application of the DND-BSA complex for isolating the substance from fungal extracts.

• Genomics & Informatics
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• v.6 no.4
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• pp.181-191
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• 2008

RAS guanyl-releasing protein 3 (RasGRP3), a member of the Ras subfamily of GTPases, functions as a guanosine triphosphate (GTP)/guanosine diphosphate (GDP)-regulated switch that cycles between inactive GDP- and active GTP-bound states during signal transduction. Various growth factors enhance hepatocellular carcinoma (HCC) proliferation via activation of the Ras/Raf-1/extracellular signal-regulated kinase (ERK) pathway, which depends on RasGRP3 activation. We investigated the relationship between polymorphisms in RasGRP3 and progression of hepatitis B virus (HBV)-infected HCC in a Korean population. Nineteen RasGRP3 SNPs were genotyped in 206 patients with chronic liver disease (CLD) and 86 patients with HCC. Our results revealed that the T allele of the rs7597095 SNP and the C allele of the rs7592762 SNP increased susceptibility to HCC (OR=1.55, p=0.04 and OR=1.81${\sim}$2.61, p=0.01${\sim}$0.03, respectively). Moreover, patients who possessed the haplotype (ht) 1 (A-T-C-G) or diplotype (dt) 1 (ht1/ht1) variations had increased susceptibility to HCC (OR=1.79${\sim}$2.78, p=0.01${\sim}$0.03). In addition, we identified an association between haplotype1 (ht1) and the age of HCC onset; the age of HCC onset are earlier in ht1 +/+ than ht1 +/- or ht1 -/- (HR=0.42${\sim}$0.66, p=0.006${\sim}$0.015). Thus, our data suggest that RasGRP3 SNPs are significantly associated with an increased risk of developing HCC.

• Journal of Life Science
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• v.27 no.10
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• pp.1191-1198
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• 2017

Vesicles and organelles are transported along microtubule and delivered to appropriate compartments in cells. The intracellular transport process is mediated by molecular motor proteins, kinesin, and dynein. Kinesin is a plus-end-directed molecular motor protein that moves the various cargoes along microtubule tracks. Kinesin 1 is first isolated from squid axoplasm is a dimer of two heavy chains (KHCs, also called KIF5s), each of which is associated with the light chain (KLC). KIF5s interact with many different binding proteins through their carboxyl (C)-terminal tail region, but their binding proteins have yet to be specified. To identify the interacting proteins for KIF5A, we performed the yeast two-hybrid screening and found a specific interaction with Ras-GTPase-activating protein (GAP) Src homology3 (SH3)-domain-binding protein 2 (G3BP2), which is involved in stress granule formation and mRNA-protein (mRNP) localization. G3BP2 bound to the C-terminal 73 amino acids of KIF5A but did not interact with the KIF5B, nor the KIF5C in the yeast two-hybrid assay. The arginine-glycine-glycine (RGG)/Gly-rich region domain of G3BP2 is a minimal binding domain for interaction with KIF5A. However, G3BP1 did not interact with KIF5A. When co-expressed in HEK-293T cells, G3BP2 co-localized with KIF5A and was co-immunoprecipitated with KIF5A. These results indicate that G3BP2, which was originally identified as a Ras-GAP SH3 domain-binding protein, is a protein that interacts with KIF5A.

• Biomedical Science Letters
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• v.15 no.4
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• pp.327-333
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• 2009

Heterotrimeric GTP binding proteins, G-proteins, mediate signal transduction generated by neurotransmitters and hormones. Among G-proteins, Go proteins are the most abundant in brain and classified as a member of Gi family. Ras-like protein in all tissues (Rit), one of the small GTPases, is a member of a Ras superfamily and identified as an important regulator of neuronal differentiation and cell transformation. Recently, we have reported that Rit functioned as a candidate downstream effector for alpha subunit of Go proteins ($Go{\alpha}$) and regulated neurite outgrowth triggered by $Go{\alpha}$ activation. In this study, we showed that the GTPase domain of $Go{\alpha}$ contributed to the direct interaction with Rit. We also demonstrated that $Go{\alpha}$ could lead to an increase of Rit activity suggesting that Rit play a role as a downstream effector of $Go{\alpha}$.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.42-42
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• 1992

ras oncogene은 암조직이나 transformed human cell line에서 거의 공통적으로 발견되는 oncogene으로서 그 product인 p2l 단백질은 C-terminal 25개의 아미노산 외에는 거의 동일한 배열을 가지고 있는 매우 conservative한 단백질이며 C-terminal cysteine이 carboxy methylation되어 있고 또한 palmitic acid와 같은 long chain fatty acid도 결합되어 있다. 보고된 바에 의하면 p21 protein의 palmitation은 ras protein의 세포막에 대한 친화력을 유지시키며 이와 같은 친화력은 cell transforming activity의 기본요건으로 알려져 있다. 이와 같은 관점에서 볼때 p21 단백질의 C-terminal processing현상을 new drug target으로, 즉 p2l 단백질의 C-terminal processing을 억제하므로서 cell transforming activity를 저해 할 수 있을 것이므로 생체내에 존재하는 p21 단백질 C-terminal processing 억제제의 identification 및 purification은 항암제 연구와 밀접한 관계가 있다. 구체적으로 farnesyl-protein transferase inhibitor 혹은 carboxyl methyl inhibitor의 identification 및 purification은 이같은 목적을 달성 할 수 있는 가능성이 크다.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.89.2-89.2
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• 2003

Ral GDP dissociation stimulator (Ral GDS) has been found to be an effector protein of Ras, and Ral, a member of small GTP-binding protein (G protein) superfamily, has been suggested to act downstream of Ras. Ral GDP dissociation stimulator-like (RGL) shares 50% amino acid identity with Ral GDP dissociation stimulator, and assumed to possess similar functional role. Using yeast two-hybrid screening, we found that dopamine D3 receptor interacts with RGL. Since RGL is known to regulate the expression of c-fos promoter, effects of D3R on gene expression of c-fos promoter was studied. (omitted)