• Title/Summary/Keyword: ISG15

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Interferon Stimulated Gene - ISG15 is a Potential Diagnostic Biomarker in Oral Squamous Cell Carcinomas

  • Laljee, Rupesh Puthenparambil;Muddaiah, Sunil;Salagundi, Basavaraj;Cariappa, Ponappa Muckatira;Indra, Adarsh Surendran;Sanjay, Venkataram;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.1147-1150
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    • 2013
  • Background: Cancer diagnostic biomarkers have a wide range of applications that include early detection of oral precancerous lesions and oral squamous cell carcinomas, and assessing the metastatic status of lesions. The interferon stimulated ISG15 gene encodes an ubiquitin-like protein, which conjugates to stabilize activation status of associated proteins. Hence a deregulated expression of ISG15 may promote carcinogenesis. Indeed overexpression of ISG15 has been observed in several cancers and hence it has been proposed as a strong candidate cancer diagnostic biomarker. Given the emerging relationship between malignant transformation and ISG15, we sought to examine the expression pattern of this gene in tumor biopsies of oral squamous cell carcinoma (OSCC) tissues collected from Indian patients. Materials and Methods: Total RNA isolated from thirty oral squamous cell carcinoma tissue biopsy samples were subjected to semi-quantitative RT-PCR with ISG15 specific primers to elucidate the expression level. Results: Of the thirty oral squamous cell carcinomas that were analyzed, ISG15 expression was found in twenty four samples (80%). Twelve samples expressed low level of ISG15, six of them expressed moderately, while the rest of them expressed very high level of ISG15. Conclusions: To the best of our knowledge, the results show for the first time an overexpression of ISG15 in up to 80% of oral squamous cell carcinoma tissues collected from Indian patients. Hence ISG15 may be explored for the possibility of use as a high confidence diagnostic biomarker in oral cancers.

Expression Analysis of Interferon-Stimulated Gene 15 in the Rock Bream Oplegnathus fasciatus against Rock Bream Iridovirus (RSIV) Challenge

  • Kim, Kyung-Hee;Yang, In Jung;Kim, Woo-Jin;Park, Choul-Ji;Park, Jong-Won;Noh, Gyeong Eon;Lee, Seunghyung;Lee, Young Mee;Hwang, Hyung Kyu;Kim, Hyun Chul
    • Development and Reproduction
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    • v.21 no.4
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    • pp.371-378
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    • 2017
  • Interferon-stimulated gene 15 (ISG15) is known to interfere with viral replication and infection by limiting the viral infection of cells. Interferon-stimulated gene 15 (ISG15) interferes with viral replication and infectivity by limiting viral infection in cells. It also plays an important role in the immune response. In this study, tissue-specific expression of ISG15 in healthy rock bream samples and spatial and temporal expression analysis of rock bream ISG15 (RbISG15) were performed following rock bream iridovirus (RSIV) infection. RbISG15 expression was significantly higher in the eye, gill, intestine, kidney, liver, muscle, spleen, and stomach, but low in the brain. There were particularly high levels of expression in the liver and muscle. RbISG15 expression was also examined in several tissues and at various times following RSIV infection. ISG15 expression increased within 3 h in the whole body and decreased at 24 h after infection. In addition, temporal expression of several tissues following RSIV infection showed a similar pattern in the muscle, kidney, and spleen, increasing at 3 h and decreasing at 72 h. These results suggest that ISG15 plays an important role in the immune response of rock bream. Overall, this study characterizes the response of RbISG15 following RSIV infection.

Molecular cloning and expression analysis of an interferon stimulated gene 15 from rock bream Oplegnathus fasciatus

  • Kim, Ju-Won;Kwon, Mun-Gyeong;Park, Myoung-Ae;Hwang, Jee-Youn;Park, Hyung-Jun;Baeck, Gun-Wook;Kim, Mu-Chan;Park, Chan-Il
    • Journal of fish pathology
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    • v.23 no.2
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    • pp.177-187
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    • 2010
  • The Interferon stimulated gene 15 (ISG15) is strongly induced in many cell types by IFNs, viral infections, and double-stranded RNA (poly I:C). The ISG15 homologue cDNA was isolated from the rock bream LPS stimulated leukocyte cDNA library. The rock bream ISG15 homologue was found to consist of 833 bp encoding 157 amino acid residues. Compared with other known ISG15 peptide sequences, the most conserved regions of the rock bream ISG15 peptide were found to be the tandem ubiquitin-like domains and a C-terminal LRLRGG conjugating motif, characteristic of mammalian and non-mammalian ISG15 proteins. Phylogenetic analysis based on the deduced amino acid sequence revealed a homologous relationship between the ISG15 sequence of rock bream and that of Atlantic salmon, Atlantic cod, northern snake head, black rockfish and olive flounder. The expression of the rock bream ISG15 molecule was induced in the peripheral blood leukocytes (PBLs) from 1 to 24 h following poly I:C stimulation, with a peak at 3 h post-stimulation. The rock bream ISG15 gene was predominantly expressed in the PBLs, spleen and gill.

Cloning and Sequence Analysis of Wild Argali ISG15 cDNA

  • Sun, Yanming;Chen, Kaili;Shen, Wen;Cui, Rupeng;Lu, Haifu
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.4
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    • pp.561-566
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    • 2014
  • The complete coding sequence of Wild Argali ISG15 cDNA was generated by rapid amplification of cDNA ends. The ISG15 cDNA was 642 bp with an open reading frame of 474 bp, which encoded a 17.47 kDa protein composed of 157 amino acids. Its amino acid sequence shared 97.9%, 80.8%, 91.4%, 94.3%, 78.3% identity with those of ISG15cDNA from Ovis aries (accession no. NM001009735.1), Capra hircus (accession no. HQ329186.1), Bos taurus (accession no. BC102318.1), Bubalus bubalis (accession no. HM543269.1), and Sus scrofa (accession no. EU647216.1), respectively. The entire coding sequence was inserted into the pET-28a vector and expressed in E. coli. The recombinant protein corresponded to the expected molecular mass of 25 kDa as judged by SDS-PAGE, and it was detected in the bacterial inclusion bodies. The expressed protein could be purified by $Ni^{2+}$ chelate affinity chromatography and the results from the lymphocyte proliferation test showed that the product could stimulate lymphocyte proliferation very well (p<0.05), which further confirmed its biological activity.

Development of crank shaft mounted ISG(Integrated Starter Generator) (크랭크축 직결형 42V기동/발전기(ISG)의 개발)

  • Bae Bon-ho;Yun Seok-Young;Sul Seung-ki
    • Proceedings of the KIPE Conference
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    • 2002.07a
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    • pp.653-656
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    • 2002
  • This paper presents the development of 15G(Integrate Starter Generator). The ISG is the crank shaft mount type and it is installed at tile flywheel. The wide operating range of ISG requires large constant power speed ratio, good overload performance and high efficiency. High saliency ratio permanent magnet motor is developed for the ISG applications and 500A MOSFET inverter is designed to derive the ISG. The characteristic of developed ISG is investigated using the special test-bed for the 42V PowerNet and the detailed results is presented

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Induction of antiviral mechanisms by interferon-related genes in rock bream (Oplegnathus fasciatus) infected with rock bream iridovirus (RBIV)

  • Myung-Hwa Jung
    • Journal of fish pathology
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    • v.36 no.2
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    • pp.213-228
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    • 2023
  • We evaluated the transcriptional response of interferon (IFN)-related genes in rock bream iridovirus (RBIV)-infected rock bream under high-, low-, or no-mortality conditions induced by different stocking water temperatures. Under the high susceptibility condition (group A, water temperature 26℃, 100% mortality), only the Mx gene was expressed early, with prolonged expression, and with heavy viral loads of approximately 106~107 major capsid protein gene copies/μL from 4 to 10 days post infection (dpi). However, IRF1, IRF3, IRF8, STAT1, ISG15, PKR, Viperin, GVIN1, IFI44, and ISG56 were activated at later time points (8 dpi) and then quickly decreased (10 dpi). For the low susceptibility condition, the water temperature was set at 23℃ for 7 days (group B) and then reduced to 17℃. Group B exhibited a 28% mortality rate, in which persistent and effective antiviral responses were observed for long periods of time. In particular, at 20 and 22 dpi, when virus replication was peaked at approximately 107/μL, the expressions of most of the IFN-related genes (IRF1, IRF3, IRF8, Mx, STAT1, ISG15, PKR, Viperin, GVIN1, IFI44, and ISG56) were significantly higher in group B than in the control group. Moreover, prolonged and higher levels of IRF3 (at least 30 dpi), IRF8 (at least 30 dpi), ISG15 (at least 30 dpi), PKR (at least 28 dpi), Viperin (at least 30 dpi), and IFI44 (at least 30 dpi) were also observed in the recovery stage of infection. Under the no-susceptibility condition at 17℃ (0% mortality), significantly elevated levels of IRF3, Mx, ISG15, and PKR were observed mostly until 20 dpi. The findings indicate that RBIV infection can induce an efficient IFN-mediated antiviral immune response in low- and no-susceptibility conditions. The findings could be valuable for effective control of viral pathogens in fish.

Regulation of Interferon-stimulated Gene (ISG)12, ISG15, and MX1 and MX2 by Conceptus Interferons (IFNTs) in Bovine Uterine Epithelial Cells

  • Kim, Min-Su;Min, Kwan-Sik;Imakawa, Kazuhiko
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.6
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    • pp.795-803
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    • 2013
  • Various endometrial genes in ruminant ungulates are regulated by conceptus interferon tau (IFNT). However, the effect of each IFNT isoform has not been carefully evaluated. In this study, the effects of 2 IFNT isoforms, paralogs found in utero, and interferon alpha (IFNA) on uterine epithelial and Mardin-Darby bovine kidney (MDBK) cells were evaluated. Expression vectors of the bovine interferon (bIFNT) genes bIFNT1, bIFNTc1, and bIFNA were constructed, and recombinant bIFNs (rbIFNs) were produced by 293 cells. Bovine uterine epithelial or MDBK cells were cultured in the presence or absence of increasing concentrations of each rbIFN for 24, 48, or 72 h. Transcript levels of the IFN-stimulated genes (ISGs) ISG12, ISG15, MX1, and MX2 were analyzed using quantitative reverse transcription-polymerase chain reaction. These messenger RNAs were up-regulated by rbIFN in a time- and concentration-dependent manner. In the epithelial cells, the ISG12 transcript level increased at 48 h after rbIFN treatment but slightly decreased at 72 h, whereas the transcript level of ISG15 increased at 24 h and was maintained through 72 h. Expressions of MX1 and MX2 increased at 72 h after rbIFN treatment. MX1 expression increased in all treatment groups, but MX2 increased only by bIFNTc1. In MDBK cells, the expression of ISG12 was increased by bIFNT1 and bIFNTc1 after 24 and 72 h; however, it was unchanged by rbIFNA. ISG15 increased following the same pattern as that seen in uterine epithelial cells, and MX1 showed a similar expression pattern. MX2 expression was increased by bIFNTc1 treatment in uterine epithelial cells, and its expression was increased by both bIFNT1 and bIFNTc1 in MDBK cells. These results show that epithelial and MDBK cell responses to IFNs differ, suggesting that IFNs possess common functions, but may have acquired different functions following gene duplication.

Interferon-Stimulated Gene 15 in the Control of Cellular Responses to Genotoxic Stress

  • Jeon, Young Joo;Park, Jong Ho;Chung, Chin Ha
    • Molecules and Cells
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    • v.40 no.2
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    • pp.83-89
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    • 2017
  • Error-free replication and repair of DNA are pivotal to organisms for faithful transmission of their genetic information. Cells orchestrate complex signaling networks that sense and resolve DNA damage. Post-translational protein modifications by ubiquitin and ubiquitin-like proteins, including SUMO and NEDD8, are critically involved in DNA damage response (DDR) and DNA damage tolerance (DDT). The expression of interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, has recently been shown to be induced under various DNA damage conditions, such as exposure to UV, camptothecin, and doxorubicin. Here we overview the recent findings on the role of ISG15 and its conjugation to target proteins (e.g., p53,$ {\Delta}Np63{\alpha}$, and PCNA) in the control of cellular responses to genotoxic stress, such as the inhibition of cell growth and tumorigenesis.

EcoMon: A System for Monitoring Eco-Driving (EcoMon: 에코 드라이빙 모니터링 시스템)

  • Han, Dongho;Kim, Sangchul
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.15 no.11
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    • pp.6830-6837
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    • 2014
  • Since the advent of global warming and energy depletion, there has been great interest in eco-driving (energy-efficient driving). In this paper, a system is proposed to monitor the idle running of an engine and steady driving for a vehicle equipped with an ISG (Idling Stop & Go system). The system consists of a G/W device to acquire the vehicle operation data, a smartphone app for monitoring eco-driving and a server system. The main contribution of this paper is that it defines the integrated functions, the architecture and operation mechanisms of a system for monitoring eco-driving including the prohibition of running idle. The system enables the users to check the idling stop times, driving speeds, fuel savings, and $CO_2$ emissions, resulting in the driving style for eco-driving. The server system, which is a part of this system, provides OpenAPI-style web services for the storage and retrieval of car operation data, which facilitates the development of applications.

CYP1B1 Activates Wnt/β-Catenin Signaling through Suppression of Herc5-Mediated ISGylation for Protein Degradation on β-Catenin in HeLa Cells

  • Park, Young-Shin;Kwon, Yeo-Jung;Chun, Young-Jin
    • Toxicological Research
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    • v.33 no.3
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    • pp.211-218
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    • 2017
  • Cytochrome P450 1B1 (CYP1B1) acts as a hydroxylase for estrogen and activates potential carcinogens. Moreover, its expression in tumor tissues is much higher than that in normal tissues. Despite this association between CYP1B1 and cancer, the detailed molecular mechanism of CYP1B1 on cancer progression in HeLa cells remains unknown. Previous reports indicated that the mRNA expression level of Herc5, an E3 ligase for ISGylation, is promoted by CYP1B1 suppression using specific small interfering RNA, and that ISGylation may be involved in ubiquitination related to ${\beta}-catenin$ degradation. With this background, we investigated the relationships among CYP1B1, Herc5, and ${\beta}-catenin$. RT-PCR and western blot analyses showed that CYP1B1 overexpression induced and CYP1B1 inhibition reduced, respectively, the expression of $Wnt/{\beta}-catenin$ signaling target genes including ${\beta}-catenin$ and cyclin D1. Moreover, HeLa cells were treated with the CYP1B1 inducer $7,12-dimethylbenz[{\alpha}]anthracene$ (DMBA) or the CYP1B1 specific inhibitor, tetramethoxystilbene (TMS) and consequently DMBA increased and TMS decreased ${\beta}-catenin$ and cyclin D1 expression, respectively. To determine the correlation between CYP1B1 expression and ISGylation, the expression of ISG15, a ubiquitin-like protein, was detected following CYP1B1 regulation, which revealed that CYP1B1 may inhibit ISGylation through suppression of ISG15 expression. In addition, the mRNA and protein expression levels of Herc5 were strongly suppressed by CYP1B1. Finally, an immunoprecipitation assay revealed a direct physical interaction between Herc5 and ${\beta}-catenin$ in HeLa cells. In conclusion, these data suggest that CYP1B1 may activate $Wnt/{\beta}-catenin$ signaling through stabilization of ${\beta}-catenin$ protein from Herc5-mediated ISGylation for proteosomal degradation.