RRC ID 34918
Author Imamura Y, Yukawa M, Ueno M, Kimura K, Tsuchiya E.
Title 3,6-Epidioxy-1,10-bisaboladiene inhibits G1 -specific transcription through Swi4/Swi6 and Mbp1/Swi6 via the Hog1 stress pathway in yeast.
Journal FEBS J.
Abstract UNLABELLED:3,6-Epidioxy-1,10-bisaboladiene (EDBD), a bisabolane sesquiterpene endoperoxide compound, was previously isolated from Cacalia delphiniifolia and C. hastata in northern Japan. EDBD has cytotoxic effects and induces apoptosis via phosphorylation of p38 mitogen-activated protein kinase in human promyelocytic leukemia HL60 cells. However, the mechanism of action of EDBD has not yet been fully elucidated. In this study, we examined the molecular mechanisms of EDBD in the budding yeast Saccharomyces cerevisiae. EDBD arrested the growth of S. cerevisiae cells by suppressing progression from the G1 phase to the S phase and from the G2 phase to the M phase. Moreover, biochemical and genetic analyses revealed that EDBD activated environmental stress-response pathways involving Hog1 and affected Cln3/G1 cyclin activity, thereby inhibiting the expression of SCB-binding factor and MCB-binding factor target genes. Our results provided important insights into the functions of EDBD in tumor cells and may facilitate the development of EDBD-based antitumor therapies.
STRUCTURED DIGITAL ABSTRACT:•Swi4 physically interacts with Swi6 by anti tag coimmunoprecipitation (View interaction).
Volume 281(20)
Pages 4612-21
Published 2014-10
DOI 10.1111/febs.12965
PMID 25112483
MeSH Blotting, Western Cyclins / genetics Cyclins / metabolism Flow Cytometry G1 Phase / drug effects* Humans Immunoprecipitation Mitogen-Activated Protein Kinases / metabolism* Nuclear Proteins / metabolism* Promoter Regions, Genetic RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Saccharomyces cerevisiae / drug effects* Saccharomyces cerevisiae / growth & development Saccharomyces cerevisiae / metabolism Saccharomyces cerevisiae Proteins / metabolism* Sesquiterpenes / pharmacology* Signal Transduction / drug effects Stress, Physiological / drug effects Transcription Factors / metabolism* Transcription, Genetic / drug effects
IF 4.53
Times Cited 2
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Yeast BYP1758