• 제목/요약/키워드: molecular functions

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Molecular imaging of polarized macrophages in tumors

  • Ran Ji Yoo;Yun-Sang Lee
    • 대한방사성의약품학회지
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    • 제7권1호
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    • pp.41-49
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    • 2021
  • Diversity and flexibility are two typical hallmarks of macrophages. Two types of macrophages, M1(classically activated macrophages) and M2(alternatively activated macrophages) exist at both ends of the commonly known macrophage polarization. M1 macrophages have inflammatory properties and are primarily responsible for defending against invading bacteria in our body. On the other hand, M2 macrophages are involved in anti-inflammatory responses and tissue remodeling. Polarized migration of macrophages is of increasing interest in regulating the initiation, generation, and resting phases of inflammatory diseases. In this review, it intend to discuss the properties and functions of tumor-associated macrophages based on polarized macrophages that affect inflammatory diseases. In addition, the purpose of this study is to investigate a molecular imaging approach that targets macrophages that affect tumor growth by controlling the polarization of macrophages that affect tumor diagnosis and treatment.

Molecular Analysis of Rice Plants Harboring an Ac/Ds Transposable Element-Mediated Gene Trapping System

  • Hang Gyeong;Mi Sook Choe;Sung-Ho Lee;Sung Han Park;Hyuk Kim;Ja Choon Koo;No Youl Kim;Su Hyun Park;Jeung Joo Lee
    • 한국식물학회:학술대회논문집
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    • 한국식물학회 1999년도 제13회 식물생명공학심포지움 New Approaches to Understand Gene Function in Plants and Application to Plant Biotechnology
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    • pp.17-20
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    • 1999
  • In rice, limited efforts have been made to identify genes by the use of insertional mutagens, especially heterologous transposons such as the maize Ac/Ds. We constructed Ac and gene trap Ds vectors and introduced them into the rice genome by Agrobacterium-mediated transformation. In this report, rice plants that contained single and simple insertions of T-DNA were analyzed in order to evaluate the gene-tagging efficiency. The 3'end of Ds was examined for putative splicing donor sites. As observed in maize, three splice donor sites were identified at the 3'end of the Ds in rice. Nearly 80% of Ds elements wered excised from the original T-DNA sites, when Ac cDNA was expressed under a CaMV 35S promoter. Repetitive ratoon culturing was performed to induce new transpositions of Ds in new plants derived from cuttings. About 30% of the plants carried at least one Ds that underwent secondary transposition in the later cultures. 8% of transposed Ds elements expressed GUS in various tissues of rice panicles. With cloned DNA adjacent to Ds, the genomic complexities of the insertion sites were examined by Southern hybridization. Half of the Ds insertion sites showed simple hybriodization patterns which could be easily utilized to locate the Ds. Our data demonstrate that the Ac/Ds mediated gene trap system could prove an excellent tool for the analysis of functions of genes in rice. We discuss genetic strategies that could be employed in a largee scale mutagenesis using a heterologous Ac/Ds family in rice.

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Investigation of function and regulation of the YB-1 cellular factor in HIV replication

  • Jung, Yu-Mi;Yu, Kyung-Lee;Park, Seong-Hyun;Lee, Seong-Deok;Kim, Min-Jeong;You, Ji-Chang
    • BMB Reports
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    • 제51권6호
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    • pp.290-295
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    • 2018
  • Y-box binding protein 1 (YB-1) is a member of the cold-shock domain (CSD) protein superfamily. It participates in a wide variety of cellular events, including transcription, RNA splicing, translation, DNA repair, drug resistance, and stress responses. We investigated putative functions of YB-1 in HIV-1 replication. Functional studies using overexpression or knockdown of YB-1 in conjunction with transfection of proviral DNA showed that YB-1 enhances virus production. We found YB-1 regulates HIV-1 production by stimulating viral transcription using HIV-1 LTR sequence U3RU5 with Luciferase assay. We also identified a specific region from amino acids 1 to 324 of YB-1 as necessary for the participation of the protein in the production of virions.

Structural Design and Characterization of a Channel-forming Peptide

  • Krittanai, Chartchai;Panyim, Sakol
    • BMB Reports
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    • 제37권4호
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    • pp.460-465
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    • 2004
  • A 16-residue polypeptide model with the sequence acetyl-YALSLAATLLKEAASL-OH was derived by rational de novo peptide design. The designed sequence consists of amino acid residues with high propensity to adopt an alpha helical conformation, and sequential order was arranged to produce an amphipathic surface. The designed sequence was chemically synthesized using a solid-phase method and the polypeptide was purified by reverse-phase liquid chromatography. Molecular mass analysis by electro-spray ionization mass spectroscopy confirmed the correct designed sequence. Structural characterization by circular dichroism spectroscopy demonstrated that the peptide adopts the expected alpha helical conformation in 50% acetonitrile solution. Liposome binding assay using Small Unilamellar Vesicle (SUV) showed a marked release of entrapped glucose by interaction between the lipid membrane and the tested peptide. The channel-forming activity of the peptide was revealed by a planar lipid bilayer experiment. An analysis of the conducting current at various applied potentials suggested that the peptide forms a cationic ion channel with an intrinsic conductance of 188 pS. These results demonstrate that a simple rational de novo design can be successfully employed to create short peptides with desired structures and functions.

The role of NUMB/NUMB isoforms in cancer stem cells

  • Choi, Hye Yeon;Seok, Jaekwon;Kang, Geun-Ho;Lim, Kyung Min;Cho, Ssang-Goo
    • BMB Reports
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    • 제54권7호
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    • pp.335-343
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    • 2021
  • Cancer stem cells (CSCs) are a subpopulation of cancer that can self-renew and differentiate into large tumor masses. Evidence accumulated to date shows that CSCs affect tumor proliferation, recurrence, and resistance to chemotherapy. Recent studies have shown that, like stem cells, CSCs maintain cells with self-renewal capacity by means of asymmetric division and promote cell proliferation by means of symmetric division. This cell division is regulated by fate determinants, such as the NUMB protein, which recently has also been confirmed as a tumor suppressor. Loss of NUMB expression leads to uncontrolled proliferation and amplification of the CSC pool, which promotes the Notch signaling pathway and reduces the expression of the p53 protein. NUMB genes are alternatively spliced to produce six functionally distinct isoforms. An interesting recent discovery is that the protein NUMB isoform produced by alternative splicing of NUMB plays an important role in promoting carcinogenesis. In this review, we summarize the known functions of NUMB and NUMB isoforms related to the proliferation and generation of CSCs.

세포내인자로서의 정교한 기능을 하는 molecular chaperone (Molecular chaperone as a sophisticated intracellular membership)

  • 권오유;송민호
    • 생명과학회지
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    • 제8권2호
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    • pp.226-226
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    • 1998
  • Molecular chaperone의 발견은 생명과학자들에게 살아있는 세포 내에서 어떻게 생체활성단백질이 만들어지고 유지되는지에 대한 자극과 함께 그것을 증명하기 위한 실험동기를 부여하였다. 초기에는 Molecular chaperone이 nucleosomes의 assembly에 관여하는 단백질을 설명하기 위하여 사용되었으나, 지금은 기본적인 세포생리기능의 하나인 단백질의 folding과 assembly를 돕는 assistant protein으로 주로 사용된다. 단백질합성 뿐만 아니라 단백질수송, oligomeric structure의 assembly와 disassembly, heat shock을 포함한 각종 내, 외부스트래스에 의해서 변성된 단백질의 세로내분화와 회복에도 Molecular chaperone이 관여하고 있다. 그러나 아직까지는 Molecular chaperone들의 3차구조와 그들간의 상호작용에 관한 정보가 부족하여 크게 진전되지 못하고 있지만, 많은 연구자에 의한 정보축적으로 인하여 빠른 시일 내에 Molecular chaperone에 세포내역할이 분명하게밝혀질 것이다.

Microbial Rhodopsins: Genome-mining, Diversity, and Structure/Function

  • Jung, Kwang-Hwan;Vishwa Trivedi;Yang, Chii-Shen;Oleg A. Sineschekov;Elena N. Spudich;John L. Spudich
    • Journal of Photoscience
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    • 제9권3호
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    • pp.45-48
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    • 2002
  • Microbial rhodopsins, photoactive 7-transmembrane helix proteins that use retinal as their chromophore, were observed initially in the Archaea and appeared to be restricted to extreme halophilic environments. Our understanding of the abundance and diversity of this family has been radically transformed by findings over the past three years. Genome sequencing of cultivated microbes as well as environmental genomics have unexpectedly revealed archaeal rhodopsin homologs in the other two domains of life as well, namely Bacteria and Eucarya. Organisms containing these homologs inhabit such diverse environments as salt flats, soil, freshwater, and surface and deep ocean waters, and they comprise a broad phylogenetic range of microbial life, including haloarchaea, proteobacteria, cyanobacteria, fungi, and algae. Analysis of the new microbial rhodopsins and their expression and structural and functional characterization reveal that they fulfill both ion transport and sensory functions in various organisms, and use a variety of signaling mechanisms. We have obtained the first crystallographic structure for a photosensory member of this family, the phototaxis receptor sensory rhodopsin II (SRII, also known as phoborhodopsin) that mediates blue-light avoidance by the haloarchaeon Natronobacterium pharaonis. The structure obtained from x-ray diffraction of 3D crystals prepared in a cubic lipid phase reveals key features responsible for its spectral tuning and its sensory function. The mechanism of SRII signaling fits a unified model for transport and signaling in this widespread family of phototransducers.

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Comparative Study of Tetrahydrothiophene and Thiophene Self Assembled Monolayers on Au(111): Structure and Molecular Orientation

  • Ito, Eisuke;Hara, Masahiko;Kanai, Kaname;Ouchi, Yukio;Seki, Kazuhiko;Noh, Jaegeun
    • Bulletin of the Korean Chemical Society
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    • 제30권8호
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    • pp.1755-1759
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    • 2009
  • Surface structure and molecular orientation of self-assembled monolayers (SAMs) formed by the spontaneous adsorption of tetrahydrothiophene (THT) and thiophene (TP) on Au(111) were investigated by means of scanning tunneling microscopy (STM) and carbon K-edge near edge X-ray absorption fine structure (NEXAFS) spectroscopy. STM imaging revealed that THT SAMs have a commensurate (3 ${\times}\;2\sqrt[]{3}$) structure containing structural defects in ordered domains, whereas TP SAMs are composed of randomly adsorbed domains and paired molecular row domains that can be described as an incommensurate packing structure. The NEXAFS spectroscopy study showed that the average tilt angle of the aliphatic THT ring and $\pi$-conjugated TP ring in the SAMs were calculated to be about $30^o\;and\;40^o$, respectively, from the surface normal. It was also observed that the $\pi$* transition peak in the NEXAFS spectrum of the TP SAMs is very weak, suggesting that a strong interaction between $\pi$-electrons and the Au surface arises during the self-assembly of TP molecules. In this study, we have clearly demonstrated that the surface structure and adsorption orientation of organic SAMs on Au(111) are strongly influenced by whether the cyclic ring is saturated or unsaturated.

Systemic and Cell-Type Specific Profiling of Molecular Changes in Parkinson's Disease

  • Lee, Yunjong
    • Interdisciplinary Bio Central
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    • 제4권3호
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    • pp.6.1-6.12
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    • 2012
  • Parkinson's disease (PD) is a complicated neurodegenerative disorder although it is oftentimes defined by clinical motor symptoms originated from age dependent and progressive loss of dopaminergic neurons in the midbrain. The pathogenesis of PD involves dopaminergic and nondopaminergic neurons in many brain regions and the molecular mechanisms underlying the death of different cell types still remain to be elucidated. There are indications that PD causing disease processes occur in a global scale ranging from DNA to RNA, and proteins. Several PD-associated genes have been reported to play diverse roles in controlling cellular functions in different levels, such as chromatin structure, transcription, processing of mRNA, translational modulation, and posttranslational modification of proteins. The advent of quantitative high throughput screening (HTS) tools makes it possible to monitor systemic changes in DNA, RNA and proteins in PD models. Combined with dopamine neuron isolation or derivation of dopamine neurons from PD patient specific induced pluripotent stem cells (PD iPSCs), HTS techonologies will provide opportunities to draw PD causing sequences of molecular events in pathologically relevant PD samples. Here I discuss previous studies that identified molecular functions in which PD genes are involved, especially those signaling pathways that can be efficiently studied using HTS methodologies. Brief descriptions of quantitative and systemic tools looking at DNA, RNA and proteins will be followed. Finally, I will emphasize the use and potential benefits of PD iPSCs-derived dopaminergic neurons to screen signaling pathways that are initiated by PD linked gene mutations and thus causative for dopaminergic neurodegneration in PD.

SMAD4 Controls Cancer Cell Metabolism by Regulating Methylmalonic Aciduria Cobalamin Deficiency (cbl) B Type

  • Song, Kyoung;Lee, Hun Seok;Jia, Lina;Chelakkot, Chaithanya;Rajasekaran, Nirmal;Shin, Young Kee
    • Molecules and Cells
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    • 제45권6호
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    • pp.413-424
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    • 2022
  • Suppressor of mothers against decapentaplegic homolog (SMAD) 4 is a pluripotent signaling mediator that regulates myriad cellular functions, including cell growth, cell division, angiogenesis, apoptosis, cell invasion, and metastasis, through transforming growth factor β (TGF-β)-dependent and -independent pathways. SMAD4 is a critical modulator in signal transduction and functions primarily as a transcription factor or cofactor. Apart from being a DNA-binding factor, the additional SMAD4 mechanisms in tumor suppression remain elusive. We previously identified methyl malonyl aciduria cobalamin deficiency B type (MMAB) as a critical SMAD4 binding protein using a proto array analysis. This study confirmed the interaction between SMAD4 and MMAB using bimolecular fluorescence complementation (BiFC) assay, proximity ligation assay (PLA), and conventional immunoprecipitation. We found that transient SMAD4 overexpression down-regulates MMAB expression via a proteasome-dependent pathway. SMAD4-MMAB interaction was independent of TGF-β signaling. Finally, we determined the effect of MMAB downregulation on cancer cells. siRNA-mediated knockdown of MMAB affected cancer cell metabolism in HeLa cells by decreasing ATP production and glucose consumption as well as inducing apoptosis. These findings suggest that SMAD4 controls cancer cell metabolism by regulating MMAB.