• BMB Reports
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• 제49권11호
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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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• 제41권5호
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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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• 제13권6호
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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.

• 대한토목학회논문집
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• 제35권6호
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• pp.1219-1228
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• 2015

면적고정형 ARF (Fixed Area ARFs)방법은 강우관측소의 지점강우를 활용하여 산정되고 있으며, 공간적 관측밀도의 제약이 정확한 ARF산정에 제약조건이 되고 있다. 본 연구에서는 레이더 강우관측을 활용하여 호우중심형의 ARF를 제시하고자 한다. 호우중심형 ARF (Storm-centered ARFs)산정 시 강우의 이동성, 방향성, 공간분포를 고려하기 위하여 강우사상별 강우형상에 따른 타원 장축의 방향성 결정, 강우형상에 따른 면적별 최적면적강우량을 산정하여 ARF를 제시하였다. 전선형에 비하여 태풍의 ARF값의 변동 폭이 작은 것을 알 수 있었고, 전선형은 지속시간에 따라 ARF가 증가하지만, 태풍의 경우에는 오히려 ARF가 감소하는 모습을 볼 수 있었다. 이 결과 지속시간이 비교적 짧은 1~3시간에서는 태풍 산바 사상의 ARF가 크게 산정되었으나, 지속시간이 긴 6~24시간에서는 ARF가 전선형 강우에 비해 작게 산정됨을 확인하였다.

• Fisheries and Aquatic Sciences
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• 제20권6호
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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.

• 한국수자원학회:학술대회논문집
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• 한국수자원학회 2015년도 학술발표회
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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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• 제13권3호
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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.

• 생명과학회지
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• 제34권5호
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• pp.333-338
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• 2024

키네신-1은 모터 도메인이 있는 두 개의 중쇄(KHC 또는 KIF5)와 모터 도메인이 없는 두 개의 경쇄(KLC)로 구성된 이형사량체 단백질이다. KIF5에는 KIF5A, KIF5B 및 KIF5C의 세 가지 subtype이 있으며, 카르복실(C)-말단 영역을 제외하고는 아미노산 상동성이 높다. KIF5A는 세포 내에서 화물을 운반하며, KIF5A의 C-말단 영역에 결합하는 매개 단백질은 키네신-1과 화물 사이를 연결한다. 키네신-1의 세포내 수송을 조절하는 단백질은 아직 충분히 확인되지 않았다. 본 연구는 리소좀의 세포 내 수송에 관여하는 ADP-ribosylation GTPase-activating protein 1 (ArfGAP1)과 KIF5A와의 결합을 확인하였다. KIF5A는 ArfGAP1의 C-말단 영역에 결합하고, ArfGAP1은 KIF5A의 C-말단 영역에 결합하지만 KIF5B, KIF5C, 키네신 경쇄 1 (KLC1) 또는 KIF3A와는 결합하지 않았다. ArfGAP 도메인을 가진 다른 동질형인 SMAP1과는 결합하지 않았다. 세포에서 KIF5A는 ArfGAP1과 같은 위치에서 발현하며, KIF5A, KIF5B 및 KLC1와 같이 면역 침전하였다. 그러나, KIF3B와는 같이 면역 침전하지 않았다. 이러한 결과들은 키네신-1은 세포내 화물 수송에서 ArfGAP1에 의해 조절될 수 있음을 시사한다.

• Neonatal Medicine
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• 제17권2호
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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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• 제12권4호
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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.