Reference - PMID:27255861 - Genetic evidence for involvement of membrane trafficking in the action of 5-fluorouracil.
Reference summary
- PubMed ID
- PMID:27255861
- Title
- Genetic evidence for involvement of membrane trafficking in the action of 5-fluorouracil.
- Authors
- Hu L, Yao F, Ma Y, Liu Q, Chen S, Hayafuji T, Kuno T, Fang Y
- Citation
- Fungal Genet Biol 2016 Aug;93:17-24
- Publication year
- 2016
- Abstract
- To identify novel genes that mediate cellular sensitivity and resistance to 5-fluorouracil (5-FU), we performed a genome-wide genetic screening to identify altered susceptibility to 5-FU by Schizosaccharomyces pombe haploid nonessential gene deletion library containing 3004 deletion mutants. We identified 50 hypersensitive and 12 resistant mutants to this drug. Mutants sensitive or resistant to 5-FU were classified into various categories based on their putative functions. The largest group of the genes whose disruption renders cells altered susceptibility to 5-FU is involved in nucleic acid metabolism, but to our surprise, the second largest group is involved in membrane trafficking. In addition, several other membrane traffic mutants examined including gdi1-i11, ypt3-i5, Δryh1, Δric1, and Δaps1 exhibited hypersensitivity to 5-FU. Furthermore, we found that 5-FU in low concentration that generally do not affect cell growth altered the localization of Syb1, a secretory vesicle SNARE synaptobrevin which is cycled between the plasma membrane and the endocytic pathway. Notably, 5-FU at such low concentration also significantly inhibited the secretion of acid phosphatase. Altogether, our findings revealed the first evidence that 5-FU influences membrane trafficking as the potential underlying mechanism of the drug action.
