title: 3,6-Epidioxy-1,10-bisaboladiene inhibits G1 -specific transcription through Swi4/Swi6 and Mbp1/Swi6 via the Hog1 stress pathway in yeast.
abstract: 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.
  •Swi4 physically interacts with Swi6 by anti tag coimmunoprecipitation (View interaction).
authors.affiliation: Department of Molecular Biotechnology, Hiroshima University, Japan; Department of Biochemistry, University of Occupational and Environmental Health, Kitakyushu City, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Imamura
authors.forename: Masashi
authors.initials: M
authors.lastname: Yukawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Ueno
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Kimura
authors.forename: Eiko
authors.initials: E
authors.lastname: Tsuchiya
mesh_terms: D015153:Blotting, Western; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D047468:Immunoprecipitation; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C576517:3,6-epidioxy-1,10-bisaboladiene; D016213:Cyclins; C083209:MBP1 protein, S cerevisiae; D009687:Nuclear Proteins; D012333:RNA, Messenger; C072981:SWI3 protein, S cerevisiae; C075111:SWI6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012717:Sesquiterpenes; D014157:Transcription Factors; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases
keywords: 3,6-epidioxy-1,10-bisaboladiene; G1 cyclin; Hog1; MCB-binding factor; SCB-binding factor