• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4301-4305
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• 2014

Tanshinone IIA is a pharmacologically active ingredient extracted from Danshen, a Chinese traditional medicine. Its molecular mechanisms are still unclear. The present study utilized computational approaches to uncover the potential targets of this compound. In this research, PharmMapper server was used as the inverse docking tool andnd the results were verified by Autodock vina in PyRx 0.8, and by DRAR-CPI, a server for drug repositioning via the chemical-protein interactome. Results showed that the retinoic acid receptor alpha ($RAR{\alpha}$), a target protein in acute promyelocytic leukemia (APL), was in the top rank, with a pharmacophore model matching well the molecular features of Tanshinone IIA. Moreover, molecular docking and drug repurposing results showed that the complex was also matched in terms of structure and chemical-protein interactions. These results indicated that $RAR{\alpha}$ may be a potential target of Tanshinone IIA for APL. The study can provide useful information for further biological and biochemical research on natural compounds.

• BMB Reports
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• v.50 no.4
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• pp.158-159
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• 2017

MicroRNAs (miRNAs) regulate gene expression by guiding the Argonaute (Ago)-containing RNA-induced silencing complex (RISC) to specific target mRNA molecules. It is well established that miRNAs are stabilized by Ago proteins, but the molecular features that trigger miRNA destabilization from Ago proteins remain largely unknown. To explore the molecular mechanisms of how targets affect the stability of miRNAs in human Ago (hAgo) proteins, we employed an in vitro system that consisted of a minimal hAgo2-RISC in HEK293T cell lysates. Surprisingly, we found that miRNAs are drastically destabilized by binding to seedless, non-canonical targets. We showed that miRNAs are destabilized at their 3' ends during this process, which is largely attributed to the conformational flexibility of the L1-PAZ domain. Based on these results, we propose that non-canonical targets may play an important regulatory role in controlling the stability of miRNAs, instead of being regulated by miRNAs.

• The Korea Genome Conference
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• 2005.09a
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• pp.52-52
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• 2005

• The Plant Pathology Journal
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• v.15 no.2
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• pp.93-98
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• 1999

• Journal of Plant Biotechnology
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• v.37 no.3
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• pp.243-249
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• 2010

Molecular farming is production of pharmaceutically and industrially important proteins in plants. Plants and plant cell culture systems have been used as bio-factory to produce recombinant proteins such as monoclonal antibodies, enzymes, vaccines, hormones, interleukins, commercial enzymes and etc. The terms molecular farming, biofarming, molecular pharming, phytomanufacturing, recombinant or plant-made industrials, planta-pharma, plant bioreactors, plant biofactory, and pharmaceutical gardening are used interchangeably. Molecular farming can provide safe and inexpensive pharmaceutical proteins as well as commercial ones. In spite of several advantages of molecular farming such as safety and inexpensive cost, there are also a couple of drawbacks in the existing technology. One of them is low expression level of target gene in plants, which has been improved by optimizing gene-based codon usage, screening of strong promoters, expression of transcription factors, subcellular targeting of target proteins, chloroplast transformation, and transient expression using viral expression system (magnifection). Some plant-based commercial proteins have already been in markets and more than twenty plant-based pharmaceuticals have been in clinical trials, from that we can expect that several plant-based pharmaceutical proteins will be seen in the markets in the near future.

• Molecules and Cells
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• v.43 no.12
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• pp.1035-1045
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• 2020

The Drosophila genome contains four low molecular weight-protein tyrosine phosphatase (LMW-PTP) members: Primo-1, Primo-2, CG14297, and CG31469. The lack of intensive biochemical analysis has limited our understanding of these proteins. Primo-1 and CG31469 were previously classified as pseudophosphatases, but CG31469 was also suggested to be a putative protein arginine phosphatase. Herein, we present the crystal structures of CG31469 and Primo-1, which are the first Drosophila LMW-PTP structures. Structural analysis showed that the two proteins adopt the typical LMW-PTP fold and have a canonically arranged P-loop. Intriguingly, while Primo-1 is presumed to be a canonical LMW-PTP, CG31469 is unique as it contains a threonine residue at the fifth position of the P-loop motif instead of highly conserved isoleucine and a characteristically narrow active site pocket, which should facilitate the accommodation of phosphoarginine. Subsequent biochemical analysis revealed that Primo-1 and CG31469 are enzymatically active on phosphotyrosine and phosphoarginine, respectively, refuting their classification as pseudophosphatases. Collectively, we provide structural and biochemical data on two Drosophila proteins: Primo-1, the canonical LMW-PTP protein, and CG31469, the first investigated eukaryotic protein arginine phosphatase. We named CG31469 as DARP, which stands for Drosophila ARginine Phosphatase.

• Journal of Digestive Cancer Research
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• v.1 no.1
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• pp.24-28
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• 2013

The five-year survival for patients with gastric cancer improved only modestly over the last 50 years. So, several studies about molecular target chemotherapy were investigated. We reviewed about molecular target chemotherapy for advanced unresectable and metastatic gastric cancer, which has developed recently. EGFR (Epidermal growth factor receptor), HER (Human epidermal growth factor receptor), VEGF (Vascular endothelial growth factor receptor) can be the target of therapy for gastric cancer. Patients with advanced gastric adenocarcinoma who are potential candidates for trastuzumab should have their tumors assayed for the presence of HER2 overexpression utilizing tumor-specific criteria and/or gene amplification. We suggest the addition of trastuzumab to chemotherapy in patients with HER2-positive tumors (as defined by 3+ immunohistochemical staining or FISH positivity), as long as they do not have a contraindication to trastuzumab. Except for trastuzumab, we summarized several studies for molecular target agents which were not validated yet.

• BMB Reports
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• v.36 no.6
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• pp.538-544
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• 2003

The hepatitis C virus (HCV) is a major causative agent of chronic hepatitis and hepatocellular carcinoma. The development of alternative antiviral therapies is warranted because current treatments for the HCV infection affect only a limited number of patients and lead to significant toxicities. The HCV genome is exclusively present in the RNA form; therefore, ribozyme strategies to target certain HCV sequences have been proposed as anti-HCV treatments. In this study, we determined which regions of the internal ribosome entry site (IRES) of HCV are accessible to ribozymes by employing an RNA mapping strategy that is based on a trans-splicing ribozyme library. We then discovered that the loop regions of the domain IIIb of HCV IRES appeared to be particularly accessible. Moreover, to verify if the target sites that were predicted to be accessible are truly the most accessible, we assessed the ribozyme activities by comparing not only the trans-splicing activities in vitro but also the trans-cleavage activities in cells of several ribozymes that targeted different sites. The ribozyme that could target the most accessible site identified by mapping studies was then the most active with high fidelity in cells as well as in vitro. These results demonstrate that the RNA mapping strategy represents an effective method to determine the accessible regions of target RNAs and have important implications for the development of various antiviral therapies which are based on RNA such as ribozyme, antisense, or siRNA.

• Proceedings of the Microbiological Society of Korea Conference
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• 2005.05a
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• pp.105-109
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• 2005

Heat Shock Transcription Factor (HSF), and the promoter heat Shock Element (HSE), are among the most highly conserved transcriptional regulatory elements in nature. HSF mediates the transcriptional response of eukaryotic cells to heat, infection and inflammation, pharmacological agents, and other stresses. While HSF is essential for cell viability in yeast, oogenesis and early development in Drosophila, extended life-span in C. elegans, and extra-embryonic development and stress resistance in mammals, little is known about its full range of biological target genes. We used whole genome analyses to identify virtually all of the direct transcriptional targets of yeast HSF, representing nearly three percent of the genomic loci. The majority of the identified loci are heat-inducibly bound by yeast HSF, and the target genes encode proteins that have a broad range of biological functions including protein folding and degradation, energy generation, protein secretion, maintenance of cell integrity, small molecule transport, cell signaling, and transcription. Approximately 30% of the HSF direct target genes are also induced by the diauxic shift, in which glucose levels begin to be depleted. We demonstrate that phosphorylation of HSF by Snf1 kinase is responsible for expression of a subset of HSF targets upon glucose starvation.

• Plant Biotechnology Reports
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• v.3 no.2
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• pp.111-126
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• 2009

MicroRNAs (miRNAs) are endogenous, non-coding, small RNA molecules consisting of 21-24 nucleotides (nts) that regulate target genes at the posttranscriptional level in plants and animals. In plants, miRNAs negatively regulate target mRNAs containing a highly complementary sequence by either mRNA cleavage or translational repression. MiRNAs are processed from single-stranded precursors containing stem-loop structures by a Dicer-like enzyme and are loaded into silencing complexes, where they act on target mRNAs. Although plant miRNAs were first reported in Arabidopsis 10 years later than animal miRNAs, numerous miRNAs have since been identified from various land plants ranging from mosses to flowering plants, and their roles in diverse aspects of plant developmental processes have been characterized. Furthermore, most of the annotated plant miRNAs are evolutionarily conserved in various plants. In particular, recent functional studies using Arabidopsis mutants have contributed a great deal of information towards establishing a framework for understanding miRNA biogenesis and functional roles. Extensive appraisal of miRNA-directed regulation during a wide array of plant development and plant responses to environmental conditions has confirmed the versatile roles of miRNAs as a key component of plant molecular biology.