Vacuolin-1 inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition
| Autor: | Ken-ichi Kazetani, Yasunori Fukuda, Masaaki Funata, Hidehisa Iwata, Junji Matsui, Osamu Sano |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Biophysics Vacuole Phosphatidylinositol 3-Kinases Biology Heterocyclic Compounds 4 or More Rings Biochemistry Cellular protein 03 medical and health sciences PIKFYVE Structural Biology Drug Discovery Autophagy Genetics Humans Protein Kinase Inhibitors Molecular Biology Cells Cultured Phosphoinositide-3 Kinase Inhibitors Drug discovery Cell Biology High-Throughput Screening Assays Cell biology Vacuolin-1 030104 developmental biology Drug Screening Assays Antitumor Lysosomes Homeostasis HeLa Cells |
| Zdroj: | FEBS Letters. 590:1576-1585 |
| ISSN: | 0014-5793 |
| Popis: | Lysosomal protein degradation via autophagy strictly regulates cellular protein homoeostasis. Herein we performed high-content screening to identify compounds that inhibit autophagy pathways. We obtained 11 hit compounds and performed cluster analysis using cellular morphological information. Vacuolin-1, which induces the formation of giant vacuoles and is a target unknown compound, clustered with the known PIKfyve inhibitor YM201636. We further confirmed that vacuolin-1 is a potent PIKfyve inhibitor, and we finally concluded that PIKfyve inhibitors are novel chemical tools for regulating autophagy. |
| Databáze: | OpenAIRE |
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