Back to Search
Start Over
Pinostrobin suppresses the Ca2+-signal-dependent growth arrest in yeast by inhibiting the Swe1-mediated G2 cell-cycle regulation.
- Source :
-
FEMS yeast research [FEMS Yeast Res] 2020 Jun 01; Vol. 20 (4). - Publication Year :
- 2020
-
Abstract
- Pinostrobin, a flavonoid compound known for its diverse pharmacological actions, including anti-leukemic and anti-inflammatory activities, has been repeatedly isolated by various screenings, but its action mechanism is still obscure. Previously, pinostrobin was rediscovered in our laboratory using a yeast-based assay procedure devised specifically for the inhibitory effect on the activated Ca2+ signaling that leads the cells to severe growth retardation in the G2 phase. Here, we attempted to identify target of pinostrobin employing the genetic techniques available in the yeast. Using various genetically engineered yeast strains in which the Ca2+-signaling cascade can be activated by the controlled expression of the various signaling molecules of the cascade, its target was narrowed down to Swe1, the cell-cycle regulatory protein kinase. The Swe1 kinase is situated at the downstream of the Ca2+-signaling cascade and downregulates the Cdc28/Clb complex by phosphorylating the Cdc28 moiety of the complex in the G2 phase. We further demonstrated that pinostrobin inhibits the protein kinase activity of Swe1 in vivo as estimated by the decreased level of Cdc28 phosphorylation at Tyr-19. Since the yeast SWE1 gene is an ortholog for the human WEE1 gene, our finding implied a potentiality of pinostrobin as the G2 checkpoint abrogator in cancer chemotherapy.<br /> (© FEMS 2020.)
- Subjects :
- Cell Cycle Proteins genetics
G2 Phase physiology
Genes, Fungal
Protein-Tyrosine Kinases genetics
Saccharomyces cerevisiae drug effects
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins genetics
Signal Transduction drug effects
Calcium metabolism
Cell Cycle Proteins antagonists & inhibitors
Cell Cycle Proteins metabolism
Flavanones pharmacology
G2 Phase genetics
Gene Expression Regulation, Fungal
Protein-Tyrosine Kinases antagonists & inhibitors
Protein-Tyrosine Kinases metabolism
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae Proteins antagonists & inhibitors
Saccharomyces cerevisiae Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1567-1364
- Volume :
- 20
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- FEMS yeast research
- Publication Type :
- Academic Journal
- Accession number :
- 32401321
- Full Text :
- https://doi.org/10.1093/femsyr/foaa026