• Title/Summary/Keyword: Molecular targets

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Human Papillomavirus Type 16/18 Oncoproteins: Potential Therapeutic Targets in Non-smoking Associated Lung Cancer

  • Zhang, Er-Ying;Tang, Xu-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5363-5369
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    • 2012
  • High-risk human papillomavirus (HPV) especially HPV-16 and HPV-18 types are speculated to be important risk factors in non-smoking associated lung cancer in Asia. Increasing evidence has demonstrated that HPV oncoproteins may contribute to lung tumorigenesis and cell transformation. Importantly, HPV 16/18 E6 and E7 oncoproteins can mediate expression of multiple target genes and proteins, such as p53/pRb, VEGF, HIF-$1{\alpha}$, cIAP-2, and hTERT, and contribute to cell proliferation, angiogenesis and cell immortalization through different signaling pathways in lung cancer. This article provides an overview of experiment data on HPV-associated lung cancer, describes the main targets on which HPV E6/E7 oncoproteins act, and further discusses the potential signaling pathways in which HPV E6/E7 oncoproteins are involved. In addition, we also raise questions regarding existing problems with the study of HPV-associated lung cancer.

Retrospective analyses of the bottleneck in purification of eukaryotic proteins from Escherichia coli as affected by molecular weight, cysteine content and isoelectric point

  • Jeon, Won-Bae
    • BMB Reports
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    • v.43 no.5
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    • pp.319-324
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    • 2010
  • Experimental bioinformatics data obtained from an E. coli cell-based eukaryotic protein purification experiment were analyzed in order to identify any bottleneck as well as the factors affecting the target purification. All targets were expressed as His-tagged maltose-binding protein (MBP) fusion constructs and were initially purified by immobilized metal affinity chromatography (IMAC). The targets were subsequently separated from the His-tagged MBP through TEV protease cleavage followed by a second IMAC isolation. Of the 743 total purification trials, 342 yielded more than 3 mg of target proteins for structural studies. The major reason for failure of target purification was poor TEV proteolysis. The overall success rate for target purification decreased linearly as cysteine content or isoelectric point (pI) of the target increased. This pattern of pI versus overall success rate strongly suggests that pI should be incorporated into target scoring criteria with a threshold value.

Protein Expression Profiling of Infected Murine Macrophage Cells (RAW 264.7) by Bacillus anthracis Spores

  • Seo Gwi-Moon;Nam Jeong-Ah;Oh Kwang-Gun;Chai Young-Gyu
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2003.05a
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    • pp.77-79
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    • 2003
  • Current therapeutic strategies far anthrax have had no significant impact on anthrax mortality over the last several decades. This study used a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) discovery platform to generate protein expression profiles in search of overexpressed proteins in murine macrophage cells (RAW264.7) which infected with Bacillus anthracis spores as potentially novel molecular targets. Two differentially expressed proteins were identified in infected murine macrophage cells as Syndapin and CDC46, respectively. Syndapins are potential links between the cortical actin cytoskeleton and endocytosis. Other two proteins were identified from murine macrophage cells infected with avirulent spores as ITBG-2 (CD18) and HSPA5, respectively. These data demonstrate the feasibility of using a MALDI-TOF platform to generate protein expression profiles and identify potential molecular targets for anthrax therapeutics.

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Systems biology of virus-host signaling network interactions

  • Xue, Qiong;Miller-Jensen, Kathryn
    • BMB Reports
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    • v.45 no.4
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    • pp.213-220
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    • 2012
  • Viruses have evolved to manipulate the host cell machinery for virus propagation, in part by interfering with the host cellular signaling network. Molecular studies of individual pathways have uncovered many viral host-protein targets; however, it is difficult to predict how viral perturbations will affect the signaling network as a whole. Systems biology approaches rely on multivariate, context-dependent measurements and computational analysis to elucidate how viral infection alters host cell signaling at a network level. Here we describe recent advances in systems analyses of signaling networks in both viral and non-viral biological contexts. These approaches have the potential to uncover virus- mediated changes to host signaling networks, suggest new therapeutic strategies, and assess how cell-to-cell variability affects host responses to infection. We argue that systems approaches will both improve understanding of how individual virus-host protein interactions fit into the progression of viral pathogenesis and help to identify novel therapeutic targets.

Chemically Induced Cellular Proteolysis: An Emerging Therapeutic Strategy for Undruggable Targets

  • Moon, Seonghyeon;Lee, Byung-Hoon
    • Molecules and Cells
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    • v.41 no.11
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    • pp.933-942
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    • 2018
  • Traditionally, small-molecule or antibody-based therapies against human diseases have been designed to inhibit the enzymatic activity or compete for the ligand binding sites of pathological target proteins. Despite its demonstrated effectiveness, such as in cancer treatment, this approach is often limited by recurring drug resistance. More importantly, not all molecular targets are enzymes or receptors with druggable 'hot spots' that can be directly occupied by active site-directed inhibitors. Recently, a promising new paradigm has been created, in which small-molecule chemicals harness the naturally occurring protein quality control machinery of the ubiquitin-proteasome system to specifically eradicate disease-causing proteins in cells. Such 'chemically induced protein degradation' may provide unprecedented opportunities for targeting proteins that are inherently undruggable, such as structural scaffolds and other non-enzymatic molecules, for therapeutic purposes. This review focuses on surveying recent progress in developing E3-guided proteolysis-targeting chimeras (PROTACs) and small-molecule chemical modulators of deubiquitinating enzymes upstream of or on the proteasome.

Outflow properties of DIGIT embedded sources

  • Kang, Seonmi;Lee, Jeong-Eun;Choi, Minho;Evans, Neal
    • The Bulletin of The Korean Astronomical Society
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    • v.38 no.1
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    • pp.51.2-51.2
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    • 2013
  • We present observational results of CO outflows towards 24 embedded young stellar objects (YSOs), which are selected from the targets of the Herschel key program, "Dust, Ice, and Gas in Time" (DIGIT). Molecular outflow activity, which is believed to have strong dependence on accretion process, is the most powerful in the early embedded phase of star formation and declines as the central protostars evolve to the main sequence stage. In order to study the relation between the CO outflows observed in low J transitions and the properties of protostars, we mapped the CO outflows of the selected targets in J=1-0 and J=2-1 with the 14-m TRAO telescope and the 6-m SRAO telescope, respectively. We also compare the CO outflow momentum fluxes with the FIR molecular line luminosities of CO, $H_2O$, OH, and OI, which were detected by the Herschel-PACS observations.

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ChimerDB - Database of Chimeric Sequences in the GenBank

  • Kim, Namshin;Shin, Seokmin;Cho, Kwang-Hwi;Lee, Sanghyuk
    • Genomics & Informatics
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    • v.2 no.2
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    • pp.61-66
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    • 2004
  • Fusion proteins resulting from chimeric sequences are excellent targets for therapeutic drug development. We developed a database of chimeric sequences by examining the genomic alignment of mRNA and EST sequences in the GenBank. We identified 688 chimeric mRNA and 20,998 chimeric EST sequences. Including EST sequences greatly expands the scope of chimeric sequences even though it inevitably accompanies many artifacts. Chimeric sequences are clustered according to the ECgene ID so that the user can easily find chimeric sequences related to a specific gene. Alignments of chimeric sequences are displayed as custom tracks in the UCSC genome browser. ChimerDB, available at http://genome.ewha.ac.kr/ECgene/ChimerDB/, should be a valuable resource for finding drug targets to treat cancers.

Autophagy: a lysosomal degradation process for cellular homeostasis and its relationship with oral squamous cell carcinoma

  • Jung, Junyoung;Kim, Joungmok;Kim, Jeong Hee
    • International Journal of Oral Biology
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    • v.46 no.2
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    • pp.74-80
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    • 2021
  • Autophagy is an evolutionarily well-conserved cellular homeostasis program that responds to various cellular stresses and degrades unnecessary or harmful intracellular materials in lysosomes. Accumulating evidence has shown that autophagy dysfunction often results in various human pathophysiological conditions, including metabolic disorders, cancers, and neurodegenerative diseases. The discovery of an autophagy machinery protein network has revealed underlying molecular mechanisms of autophagy, and advances in the understanding of its regulatory mechanism have provided novel therapeutic targets for treating human diseases. Recently, reports have emerged on the involvement of autophagy in oral squamous cell carcinoma (OSCC). Although the role of autophagy in cancer therapy is controversial, the beneficial use of the induction of autophagic cell death in OSCC has drawn significant attention. In this review, the types of autophagy, mechanism of autophagosome biogenesis, and modulating molecules and therapeutic candidates affecting the induction of autophagic cell death in OSCC are briefly described.

Calyxaprenols A-D, New Merohexaprenoid Metabolites from the Marine Sponge Calyx sp.

  • Kim, Chang-Kwon;Gustafson, Kirk R.
    • Natural Product Sciences
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    • v.26 no.4
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    • pp.303-310
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    • 2020
  • Four new merohexapenoids named calyxaprenols A-D (1 - 4), together with the known compound haliclotriol A (5), have been isolated from the marine sponge Calyx sp. which was collected from the southwest islands of Palau. Based on comprehensive spectroscopic analyses, calyxaprenols A (1) and B (2) were determined to be pentacyclic hexaprenoids that are appended to a glycolic acid-substituted phenol moiety, whereas calyxaprenols C (3) and D (4) possess a tricyclic hexaprenoid skeleton joined to a hydroquinone ring. Identification of new merohexaprenoids from a Calyx sponge expands the known taxonomic distribution of this sparsely distributed class of marine metabolites and increases the chemical diversity described for this genus of marine sponge.

Proteomic studies of putative molecular signatures for biological effects by Korean Red Ginseng

  • Lee, Yong Yook;Seo, Hwi Won;Kyung, Jong-Su;Hyun, Sun Hee;Han, Byung Cheol;Park, Songhee;So, Seung Ho;Lee, Seung Ho;Yi, Eugene C.
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.666-675
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    • 2019
  • Background: Korean Red Ginseng (KRG) has been widely used as an herbal medicine to normalize and strengthen body functions. Although many researchers have focused on the biological effects of KRG, more studies on the action mechanism of red ginseng are still needed. Previously, we investigated the proteomic changes of the rat spleen while searching for molecular signatures and the action mechanism of KRG. The proteomic analysis revealed that differentially expressed proteins (DEPs) were involved in the increased immune response and phagocytosis. The aim of this study was to evaluate the biological activities of KRG, especially the immune-enhancing response of KRG. Methods: Rats were divided into 4 groups: 0 (control group), 500, 1000, and 2000 mg/kg administration of KRG powder for 6 weeks, respectively. Isobaric tags for relative and absolute quantitation was performed with Q-Exactive LC-MS/MS to compare associated proteins between the groups. The putative DEPs were identified by a current UniProt rat protein database search and by the Gene Ontology annotations. Results: The DEPs appear to increase the innate and acquired immunity as well as immune cell movement. These results suggest that KRG can stimulate immune responses. This analysis refined our targets of interest to include the potential functions of KRG. Furthermore, we validated the potential molecular targets of the functions, representatively LCN2, CRAMP, and HLA-DQB1, by Western blotting. Conclusion: These results may provide molecular signature candidates to elucidate the mechanisms of the immune response by KRG. Here, we demonstrate a strategy of tissue proteomics for the discovery of the molecular function of KRG.