• BMB Reports
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• v.49 no.11
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• pp.598-606
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• 2016

ARF is an alternative reading frame product of the INK4a/ARF locus, inactivated in numerous human cancers. ARF is a key regulator of cellular senescence, an irreversible cell growth arrest that suppresses tumor cell growth. It functions by sequestering MDM2 (a p53 E3 ligase) in the nucleolus, thus activating p53. Besides MDM2, ARF has numerous other interacting partners that induce either cellular senescence or apoptosis in a p53-independent manner. This further complicates the dynamics of the ARF network. Expression of ARF is frequently disrupted in human cancers, mainly due to epigenetic and transcriptional regulation. Vigorous studies on various transcription factors that either positively or negatively regulate ARF transcription have been carried out. However, recent focus on posttranslational modifications, particularly ubiquitination, indicates wider dynamic controls of ARF than previously known. In this review, we discuss the role and dynamic regulation of ARF in senescence and cancer.

• Molecules and Cells
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• v.41 no.5
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• pp.381-389
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• 2018

ARF is a tumor suppressor protein that has a pivotal role in the prevention of cancer development through regulating cell proliferation, senescence, and apoptosis. As a factor that induces senescence, the role of ARF as a tumor suppressor is closely linked to the p53-MDM2 axis, which is a key process that restrains tumor formation. Thus, many cancer cells either lack a functional ARF or p53, which enables them to evade cell oncogenic stress-mediated cycle arrest, senescence, or apoptosis. In particular, the ARF gene is a frequent target of genetic and epigenetic alterations including promoter hyper-methylation or gene deletion. However, as many cancer cells still express ARF, pathways that negatively modulate transcriptional or post-translational regulation of ARF could be potentially important means for cancer cells to induce cellular proliferation. These recent findings of regulators affecting ARF protein stability along with its low levels in numerous human cancers indicate the significance of an ARF post-translational mechanism in cancers. Novel findings of regulators stimulating or suppressing ARF function would provide new therapeutic targets to manage cancer- and senescence-related diseases. In this review, we present the current knowledge on the regulation and alterations of ARF expression in human cancers, and indicate the importance of regulators of ARF as a prognostic marker and in potential therapeutic strategies.

• Journal of Microbiology and Biotechnology
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• v.13 no.6
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• pp.897-905
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• 2003

Phospholipase D (PLD) and ADP-ribosylation factor (ARF) were partially purified on a series of column chromatography, and their biochemical properties were characterized to understand the regulatory mechanism of PLD activation by ARF protein in the antigen-induced immune responses in guinea pigs. Heparin Sepharose and high-Q Sepharose column chromatographies were used for the purification of PLD, and Sephadex G-25, DEAE Sephacel, Source 15 PHE (HIC), Superdex-75, and Uno-Q column chromatographies were used for the purification of ARF. The purified PLD and ARF proteins were identified with anti-rabbit PLD- or ARF-specific antibodies, showing about 64 or 85 kDa for the molecular mass of PLD and 29 or 35 kDa for the sizes of ARF. Partial cDNA of ARF3 was cloned by RT-PCR in guinea pig lung tissue and its nucleotides and amino acids were sequenced. Guinea pig ARF3 showed 92% of nucleotides sequence identity and 100% of amino acid sequence homology with human ARF3. The ARF-regulated PLD activity was measured in the oleate or ARFs-containing mixed lipid vesicles. The purified and recombinant ARF (rARF) activities were assessed with the $GTP{\gamma}S$ binding assay. The PLD activity was induced by oleate in a dose-dependent manner. The purified ARF and recombinant ARF3 increased PLD activity in guinea pig lung tissues. These data show that the activity of membrane-bound PLD can be regulated by the cytosolic ARF proteins, suggesting that ARF proteins in guinea pig lung can act as a regulatory factor in controlling the PLD activity in allergic reaction.

• KSCE Journal of Civil and Environmental Engineering Research
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• v.35 no.6
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• pp.1219-1228
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• 2015

The Fixed Area ARFs (Area Reduction Factors) method has limitations in providing exact information about spatial distribution due to the lack of enough density of rain gauge stations. In this study the storm-centered ARF was evaluated between frontal and typhoon storm events utilizing radar precipitation. In estimating storm-centered ARFs, in order to consider the horizontal advection, direction, and spatial distribution of rain cells, the rotational angle of rainfall of each rainfall event and the optimum areal rainfall within the spatial rain cell envelope was taken into account. Compared with the frontal storm, the ARF of typhoon storm shows narrow range of variability. It is noted that the ARFs of frontal storm increases with the rainfall duration, but those of typhoon storm shows opposite pattern. As a result the typhoon ARFs appear greater than frontal ARFs for 1~3 hours of duration, but less for more than 6 hours of duration.

• Fisheries and Aquatic Sciences
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• v.20 no.6
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• pp.10.1-10.7
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• 2017

Small GTPases are well known as one of the signal transduction factors of immune systems. The ADP-ribosylation factors (ARFs) can be classified into three groups based on the peptide sequence, protein molecular weight, gene structure, and phylogenetic analysis. ARF1 recruits coat proteins to the Golgi membranes when it is bound to GTP. The class I duplicated ARF gene was cloned and characterized from the olive flounder (Paralichthys olivaceus) for this study. PoARF1b contains the GTP-binding motif and the switch 1 and 2 regions. PoARF1b and PoARF1b mutants were transfected into a Hirame natural embryo cell to determine the distribution of its GDP/GTP-bound state; consequently, it was confirmed that PoARF1b associates with the Golgi body when it is in a GTP-binding form. The results of the qPCR-described PoARF1b were expressed for all of the P. olivaceus tissues. The authors plan to study the gene expression patterns of PoARF1b in terms of immunity challenges.

• Proceedings of the Korea Water Resources Association Conference
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• 2015.05a
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• pp.427-427
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• 2015

The storm water management and drainage relation are the key variable that plays a vital role on hydrological design and risk analysis. These require knowledge about spatial variability over a specified area. Generally, design rainfall values are expressed from the fixed point rainfall, which is depth at a specific location. Concurrently, determine the areal rainfall amount is also very important. Therefore, a spatial rainfall interpolation (point rainfall converting to areal rainfall) can be solved by areal reduction factor (ARF) estimation. In mainland of South Korea, for dam design and its operation, public safety, other surface water projects concerned about ARF for extreme hydrological events. In spite of the long term average rainfall (2,061 mm) and increasing extreme rainfall events, ARF estimation is also essential for Jeju Island's water control structures. To meet up this purpose, five fixed rainfall stations of automatic weather stations (AWS) near the "Hancheon Stream Watershed" area has been considered and more than 50 years of high quality rainfall data have been analyzed for estimating design rainfall. The relationship approach for the 24 hour design storm is assessed based on ARF. Furthermore, this presentation will provide an outline of ARF standards that can be used to assist the decision makers and water resources engineers for other streams of Jeju Island.

• Archives of Pharmacal Research
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• v.13 no.3
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• pp.233-239
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• 1990

The efect of acute renal failure (ARF) on the pharmacokinetics o sulfobromophthalein (BSP) was investigated in order to elucidate if renal failure modifies the hepatic metabolism of drugs. ARF was induced by intravenous (iv) injection of uranyl nitrate (UN) to rats (5 mg/kg) five days before the experiment. Area under the plasma concentration-time curve (AUC)of BSP after portal vein (pv) injection increased by 2-fold and total body clearance ($CL_1$) decreased one half (p <0.01) in UN-induced ARF (UN-ARF) rate compared to the control rats. But the plasma disappearance of BSP after iv injection did not differ significantly between control and UN-ARF rats. Since BSP is excreted via the liver, $CL_1$ represented the approximate hepatic clearance of BSP. Therefore, the decrease in $CL_1$ represented the approximate hepatic clearance of BSP. Therefore, the decrease in $CL_1$ represents a decrease in hepatic intrinsic clearance ($CL_{int}$) for BSP since plasma free fraction ($f_p$) of BSP was not affected by UN-ARF. The content of hepatic cytoplasmic Y-protein, which catalyzes BSP-glutathione conjugation and limits the trasfer of BSP from blood to bile, increased significantly (p < 0.01), however its binding activity (BA) for BSP was decreased significantly (p <0.01) by UN-ARF. The decrease in $CL_{int}$might have some correlation with the changed characteristics of hepatic Y-protein, specifically its decreased BA for BSP.

• Journal of Life Science
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• v.34 no.5
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• pp.333-338
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• 2024

Kinesin-1 is a heterotetrameric protein composed of two heavy chains (KHCs, also known as KIF5s) with a motor domain and two light chains (KLCs) without a motor domain. KIF5 has three subtypes, namely, KIF5A, KIF5B, and KIF5C, which share high amino acid homology except in their carboxy (C)-terminal region. KIF5A is responsible for transporting cargo within the cell. The adaptor proteins that bind to the C-terminal region of KIF5A mediate between kinesin-1 and cargo. However, the proteins regulating the intracellular cargo transport of kinesin-1 have not yet been fully identified. In this study, we identified ADP-ribosylation factor GTPase-activating protein 1 (ArfGAP1), which is involved in the intracellular trafficking of lysosomes, as a binding partner of KIF5A. KIF5A binds to the C-terminal region of ArfGAP1, and ArfGAP1 binds to the C-terminal region of KIF5A but does not interact with KIF5B, KIF5C, kinesin light chain 1 (KLC1), or KIF3A. When co-expressed in mammalian cells, ArfGAP1 co-localized with KIF5A and co-immunoprecipitated with KIF5A, KIF5B, and KLC1, but not with KIF3B. These results suggest that kinesin-1 may be regulated by ArfGAP1 in the intracellular transport of cargo.

• Neonatal Medicine
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• v.17 no.2
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• pp.168-180
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• 2010

Acute renal failure (ARF) is common in the neonatal period, however, there are no uniform treatment strategies of ARF. The main treatment strategies are conservative management including medical treatment and the renal replacement therapy. Because ARF in the newborn is commonly acquired by hypoxic ischemic injury and toxic insults, removal of all the offending causes is important. Aminoglycoside, indomethacin, and amphotericin-B are the most common nephrotoxic drugs of ARF. To relieve the possible prerenal ARF, initial fluid challenge can be followed by diuretics. If there is no response, fluid restriction and correction of electrolyte imbalance should begin. Adequate nutritional support and drug dosing according to the pharmacokinetics of such drugs will be difficult problems. Renal replacement therapies may be provided by peritoneal dialysis, intermittent hemodialysis, or hemofiltration. New promising agents, bioartificial kidney, and stem cell will enable us to extend our therapeutic repertoire.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.149-153
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• 2008

Endothelin-1 (ET-1) is unequivocally elevated in the kidney with ischemic acute renal failure (ARF), whereas ET receptors ($ET_AR$ and $ET_BR$) are variably expressed. Although renal functional and structural changes are similar between ischemic and nephrotoxic ARF, there are few reports on the alteration in the ET system in nephrotoxic ARF. This study was, therefore, undertaken to investigate changes in renal expression of ET-l and its receptors in nephrotoxic ARF induced by cisplatin. Mice were intraperitoneally injected with 16 mg of cisplatin/kg at a single dose, and the expression of mRNA and protein was then quantified by real-time RT-PCR and Western blot, respectively. Immunohistochemistry was conducted for localization. Three days after treatment, ET-1 transcript in cisplatin-treated mice was thirteen times higher than that in controls, whereas ET-1 peptide was increased by 1.5-fold. Cisplatin caused a 2-fold increase in the levels of ETAR mRNA and protein. Most of the increased immunoreactive ET-1 and ETAR were localized in damaged tubules. Neither the expression of ETBR mRNA nor the abundance and immunoreactive level of ETBR protein were changed. The findings suggest that the individual components of the renal ET system are differentially regulated in cisplatin-induced nephrotoxic ARF.