Novel Small-Molecule Compounds That Affect Cellular Morphogenesis in Yeast and Mammalian Cells
スポンサーリンク
概要
- 論文の詳細を見る
Drugs affecting cellular morphological changes leading to tumor cell migration and invasion are desirable for cancer therapy. In the present study, we screened for small-molecule compounds that affect the cellular morphology of both unicellular yeast and mammalian HEK293 cells to identify drug candidates. The yeast formin protein Bni1 and Src homology 3 (SH3)-pleckstrin homology (PH) domain protein Boi1, which are required for proper morphogenesis, cause growth defects when overexpressed in yeast. Using this system, we screened a chemical library consisting of 8000 compounds to identify drug candidates that suppress these growth defects. None of the screened compounds induced morphological changes in vegetatively growing yeast cells, but several compounds had inhibitory effects on pheromone-induced projection formation and actin localization, suggesting that these compounds affected a specific stage of morphogenesis. Five of the compounds also induced morphological changes in mammalian HEK293 cells. Among the identified compounds, BTB03156, 2-[(4-chlorophenyl)sulfonyl]-1-methyl-3,5-dinitrobenzene, and BTB02467, 1-[(4-chlorophenyl)sulfonyl]-2-nitro-4-(trifluoromethyl)benzene, although they have similar structures, displayed differing effects on the yeast growth defects caused by latrunculin A, an actin polymerization inhibitor. The chemical library compounds identified using this in vivo screening approach are simple, cell-permeable molecules, and therefore may be useful in the development of therapeutic drugs for cancer metastasis and other actin-related diseases.
著者
-
Akada Rinji
Department Of Applied Chemistry And Chemical Engineering Faculty Of Engineering Yamaguchi University
-
Hoshida Hisashi
Department Of Applied Chemistry And Chemical Engineering Faculty Of Engineering Yamaguchi University
-
Kitagawa Takao
Department Of Applied Molecular Bioscience Yamaguchi University Graduate School Of Medicine
-
Watanapokasin Ramida
Department Of Biochemistry Faculty Of Medicine Srinakharinwirot University
-
NAKAMURA Mikiko
Innovation Center, Yamaguchi University
-
FUKUNAGA Tomoaki
Department of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine
関連論文
- Self-cloning Yeast Strains Containing Novel FAS2 Mutations Produce a Higher Amount of Ethyl Caproate in Japanese Sake
- Isolation of Five Laccase Gene Sequences from the White-Rot Fungus Trametes sanguinea by PCR, and Cloning, Characterization and Expression of the Laccase cDNA in Yeasts
- Detection of a Point Mutation in FAS2 Gene of Sake Yeast Strains by Allele-Specific PCR Amplification
- Construction of Recombinant Sake Yeast Containing a Dominant FAS2 Mutation without Extraneous Sequences by a Two-Step Gene Replacement Protocol
- Copper-Dependent Production of a Pycnoporus coccineus Extracellular Laccase in Aspergillus oryzae and Saccharomyces cerevisiae
- A Dominant Mutation Which Suppresses Deletion Mutations in the Secretory Signal Sequences of Glucoamylase from the Yeast Saccharomyces diastaticus(Biological Chemistry)
- Construction and Characterization of Mutant Glucoamylases from the Yeast Saccharomycopsis fibuligera(Biological Chemistry)
- Genes Required for Transcription of STA1 encoding an Extracellular Glucoamylase in the Yeast Saccharomyces(Biological Chemistry)
- Upstream Regions of the Yeast Glucoamylase Gene Which Are Required for Efficient Transcription(Biological Chemistry)
- Isolation of a Novel Mutant Strain of Saccharomyces cerevisiae by an Ethyl Methane Sulfonate-Induced Mutagenesis Approach as a High Producer of Bioethanol(MICROBIAL PHYSIOLOGY AND BIOTECHNOLOGY)
- Screening of Drugs That Suppress Ste11 MAPKKK Activation in Yeast Identified a c-Abl Tyrosine Kinase Inhibitor
- Development of a Novel Functional High-Throughput Screening System for Pathogen Effectors in the Yeast Saccharomyces cerevisiae
- Combinatorial Gene Overexpression and Recessive Mutant Gene Introduction in Sake Yeast
- Cloning of a Gene Coding for Rhodotorucin A, a Farnesyl Peptide Mating Pheromone of Rhodosporidium toruloides(Biological Chemistry)
- Construction of Flocculent Kluyveromyces marxianus Strains Suitable for High-Temperature Ethanol Fermentation
- Genetically Modified Industrial Yeast Ready for Application(BREWING AND FOOD TECHNOLOGY)
- Inostamycin enhanced TRAIL-induced apoptosis through DR5 upregulation on the cell surface
- Novel Small-Molecule Compounds That Affect Cellular Morphogenesis in Yeast and Mammalian Cells