Cloning and identification of<i>NS5ATP2</i>gene and its spliced variant transactivated by hepatitis C virus non-structural protein 5A

Yang, Qian; Cheng, Jun; Liu, Yan; Yuan, Hong; Wang, Jianjun; Zhang, Shulin

doi:10.3748/wjg.v10.i12.1735

Cited by 9 publications

(8 citation statements)

References 28 publications

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“…We thus retained two candidates. The highest occurring clone, from both libraries, corresponded to the NS5A-TP2 protein recently discovered through a systematic search for genes that are transactivated by the non-structural NS5A protein from hepatitis C virus (22). No biological knowledge is currently available for this protein.…”

Section: Figmentioning

confidence: 99%

“…We have retained NS5A-TP2 and CNA as two strong target candidates. No biological information is currently available for NS5A-TP2 except that its coding gene is transactivated by the non-structural NS5A protein from hepatitis C virus (22). In contrast, calcineurin (of which CNA is the catalytic subunit) is a well studied protein phosphatase that plays a key role in coupling Ca 2ϩ signaling to cellular responses (for a review, see Ref.…”

Section: Screening Of Antiproliferative Peptide Aptamersmentioning

confidence: 99%

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An Antiproliferative Genetic Screening Identifies a Peptide Aptamer That Targets Calcineurin and Up-regulates Its Activity

Chassey

Mikaélian²,

Mathieu³

et al. 2007

Molecular & Cellular Proteomics

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Section: Figmentioning

confidence: 99%

Section: Screening Of Antiproliferative Peptide Aptamersmentioning

confidence: 99%

An Antiproliferative Genetic Screening Identifies a Peptide Aptamer That Targets Calcineurin and Up-regulates Its Activity

Chassey

Mikaélian²,

Mathieu³

et al. 2007

Molecular & Cellular Proteomics

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“…Interestingly, R5G42 has dual target specificity. It binds to CnA, a serine/threonine protein phosphatase (17), and to NS5A-TP2, a protein trans-activated by hepatitis C virus NS5A (12). The objective of the present study was to identify peptide aptamers specific for either CnA or NS5A-TP2 in order to be able to further dissect their roles in signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Two proteins have been isolated as targets of this peptide aptamer: calcineurin A (CnA) 1 and hepatitis C virus NS5A-transactivated protein 2 (NS5A-TP2) (12). The present study aimed at investigating the contribution of both interactions to cell proliferation.…”

mentioning

confidence: 99%

Calcineurin A versus NS5A-TP2/HD Domain Containing 2: A Case Study of Site-directed Low-frequency Random Mutagenesis for Dissecting Target Specificity of Peptide Aptamers

Dibenedetto¹,

Cluet²,

Stébé³

et al. 2013

Molecular & Cellular Proteomics

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We previously identified a peptide aptamer (named R5G42) via functional selection for its capacity to slow cell proliferation. A yeast two-hybrid screen of human cDNA libraries, using R5G42 as “bait,” allowed the identification of two binding proteins with very different functions: calcineurin A (CnA) (PP2B/PPP3CA), a protein phosphatase well characterized for its role in the immune response, and NS5A-TP2/HD domain containing 2, a much less studied protein induced subsequent to hepatitis C virus non-structural protein 5A expression in HepG2 hepatocellular carcinoma cells, with no known activity. Our objective in the present study was to dissect the dual target specificity of R5G42 in order to have tools with which to better characterize the actions of the peptide aptamers toward their individual targets. This was achieved through the selection of random mutants of the variable loop, derived from R5G42, evaluating their specificity toward CnA and NS5A-TP2 and analyzing their sequence. An interdisciplinary approach involving biomolecular computer simulations with integration of the sequence data and yeast two-hybrid binding phenotypes of these mutants yielded two structurally distinct conformers affording the potential molecular basis of the binding diversity of R5G42. Evaluation of the biological impact of CnA- versus NS5A-TP2-specific peptide aptamers indicated that although both contributed to the anti-proliferative effect of R5G42, CnA-binding was essential to stimulate the nuclear translocation of nuclear factor of activated T cells, indicative of the activation of endogenous CnA. By dissecting the target specificity of R5G42, we have generated novel tools with which to study each target individually. Apta-C8 is capable of directly activating CnA independent of binding to NS5A-TP2 and will be an important tool in studying the role of CnA activation in the regulation of different signaling pathways, whereas Apta-E1 will allow dissection of the function of NS5A-TP2, serving as an example of the usefulness of peptide aptamer technology for investigating signaling pathways.

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“…The nucleolar and coiled-body phosphoprotein 1 (NOLC1, also called Nopp140 or NS5ATP13) is a family of proteins which is characterized by a conserved C-terminal SRP40 domain (6). NOLC1 is a phosphoprotein composed of N-and C-terminal domains and a unique central repeated domain consisting of alternating acidic and basic amino acid clusters and localized in the nucleolus (7).…”

Section: Introductionmentioning

confidence: 99%

Methylation of nucleolar and coiled-body phosphoprotein 1 is associated with the mechanism of tumorigenesis in hepatocellular carcinoma

et al. 2013

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Nucleolar and coiled-body phosphoprotein 1 (NOLC1) plays an essential role in the synthesis of rRNA and the biosynthesis of ribosomes. Previous studies suggest that NOLC1 is crucial for normal cell growth, and plays a role in the regulation of tumorigenesis of nasopharyngeal carcinoma (NPC) and demonstrate that both NOLC1 and tumor protein 53 work synergistically to activate the MDM2 promoter in NPC cells. Yet, the functioning of NOLC1 in liver cancer remains unknown. The aim of the present study was to understand how the NOLC1 gene is regulated in liver carcinogenesis. In this study, we showed that NOLC1 was silenced or downregulated in liver tumor tissues when compared with that in the matched non-cancer tissues. In addition, human hepatoma cells weakly expressed NOLC1, whereas cultured human normal liver cell lines expressed abundant levels. The hypermethylation status in the promoter CpG1 start region appeared to be correlated with the NOLC1 expression levels in liver cell lines or liver normal and tissue specimens. We found that four CpG dinucleotides were located at the CpG1 start region. Further molecular analysis of mutagenesis indicated that the four CpG dinucleotides play a role in the promoter activity of the NOLC1 gene. The expression of NOLC1 and DNA methylation of its promoter affected cell proliferation and apoptosis. The expression of NOLC1 in hepatoma cell lines was restored following exposure to the demethylation agent, 5-azacytidine. Low expression of NOLC1 in hepatoma cell lines and liver cancer tissues was associated with cyclin D3. In conclusion, our study demonstrated that DNA methylation is a key mechanism of silenced NOLC1 expression in human hepatocellular carcinoma cells, and NOLC1 gene hypermethylation of the four CpG dinucleotides is a potential biomarker for hepatocellular carcinoma.

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Cloning and identification ofNS5ATP2gene and its spliced variant transactivated by hepatitis C virus non-structural protein 5A

Cited by 9 publications

References 28 publications

An Antiproliferative Genetic Screening Identifies a Peptide Aptamer That Targets Calcineurin and Up-regulates Its Activity

An Antiproliferative Genetic Screening Identifies a Peptide Aptamer That Targets Calcineurin and Up-regulates Its Activity

Calcineurin A versus NS5A-TP2/HD Domain Containing 2: A Case Study of Site-directed Low-frequency Random Mutagenesis for Dissecting Target Specificity of Peptide Aptamers

Methylation of nucleolar and coiled-body phosphoprotein 1 is associated with the mechanism of tumorigenesis in hepatocellular carcinoma

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