論文 - 詳細
| RRC ID | 12650 |
|---|---|
| 著者 | Sekigawa M, Kunoh T, Wada S, Mukai Y, Ohshima K, Ohta S, Goshima N, Sasaki R, Mizukami T. |
| タイトル | Comprehensive screening of human genes with inhibitory effects on yeast growth and validation of a yeast cell-based system for screening chemicals. |
| ジャーナル | J Biomol Screen |
| Abstract |
To evaluate yeast as a high-throughput cell-based system for screening chemicals that may lead to drug development, 10,302 full-length human cDNAs (~50% of the total cDNAs) were introduced into yeast. Approximately 5.6% (583 clones) of the cDNAs repressed the growth of yeast. Notably, ~25% of the repressive cDNAs encoded uncharacterized proteins. Small chemicals can be readily surveyed by monitoring their restorative effects on the growth of yeast. The authors focused on protein kinases because protein kinases are involved in various diseases. Among 263 protein kinase cDNAs (~50% of the total) expressed in yeast, 60 cDNAs (~23%), including c-Yes, a member of the Src tyrosine kinase family, inhibited the growth of yeast. Known inhibitors for protein kinases were examined for whether they reversed the c-Yes-induced inhibition of the yeast growth. Among 85 inhibitors tested, 6 compounds (PP2, PP1, SU6656, purvalanol, radicicol, and geldanamycin) reversed the inhibition, indicating a high specificity sufficient for validating this screening system. Human c-Yes was found to interact with Hsc82, one of the yeast chaperones. Radicicol and geldanamycin probably exerted their actions through interactions with Hsc82. These results indicate that when human proteins requiring molecular chaperones for their activities are subjected to the yeast screening system, 2 groups of chemicals may be found. The actions of one group are exerted through direct interactions with the human proteins, whereas those of the other group are mediated through interactions with chaperones. |
| 巻・号 | 15(4) |
| ページ | 368-78 |
| 公開日 | 2010-4-1 |
| DOI | 10.1177/1087057110363822 |
| PII | 1087057110363822 |
| PMID | 20237203 |
| MeSH | Benzoquinones / pharmacology Cell Membrane Permeability / drug effects Cell Membrane Permeability / genetics DNA, Complementary / genetics Drug Evaluation, Preclinical / methods* Enzyme Stability / drug effects Gene Deletion Genes* High-Throughput Screening Assays / methods* Humans Indoles / pharmacology Lactams, Macrocyclic / pharmacology Macrolides / pharmacology Molecular Chaperones / metabolism Protein Binding / drug effects Protein Kinase Inhibitors / pharmacology Protein Kinases / metabolism Proto-Oncogene Proteins c-yes / antagonists & inhibitors Purines / pharmacology Pyrazoles / pharmacology Pyrimidines / pharmacology Reproducibility of Results Saccharomyces cerevisiae / cytology Saccharomyces cerevisiae / drug effects* Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae / growth & development* Sulfonamides / pharmacology Transformation, Genetic |
| IF | 2.297 |
| 引用数 | 6 |
| WOS 分野 | BIOTECHNOLOGY & APPLIED MICROBIOLOGY CHEMISTRY, ANALYTICAL BIOCHEMICAL RESEARCH METHODS |
| オルトメトリクス指標 |
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 酵母 | NA |