title: The Protein Kinase A Pathway Regulates Zearalenone Production by Modulating Alternative ZEB2 Transcription.
abstract: Zearalenone (ZEA) is an estrogenic mycotoxin that is produced by several Fusarium species, including Fusarium graminearum. One of the ZEA biosynthetic genes, ZEB2, encodes two isoforms of Zeb2 by alternative transcription, forming an activator (Zeb2L-Zeb2L homooligomer) and an inhibitor (Zeb2L-Zeb2S heterodimer) that directly regulate the ZEA biosynthetic genes in F. graminearum. Cyclic AMP-dependent protein kinase A (PKA) signaling regulates secondary metabolic processes in several filamentous fungi. In this study, we investigated the effects of the PKA signaling pathway on ZEA biosynthesis. Through functional analyses of PKA catalytic and regulatory subunits (CPKs and PKR), we found that the PKA pathway negatively regulates ZEA production. Genetic and biochemical evidence further demonstrated that the PKA pathway specifically represses ZEB2L transcription and also takes part in posttranscriptional regulation of ZEB2L during ZEA production. Our findings reveal the intriguing mechanism that the PKA pathway regulates secondary metabolite production by reprograming alternative transcription.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.|Center for Food and Bioconvergence, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Ae Ran
authors.initials: AR
authors.lastname: Park
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Minmin
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.|Center for Food and Bioconvergence, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Hokyoung
authors.initials: H
authors.lastname: Son
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Yin-Won
authors.initials: YW
authors.lastname: Lee
mesh_terms: D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005670:Fusarium / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D005800:Genes, Fungal; D009183:Mycotoxins / Q000032:analysis; D020033:Protein Isoforms; D017384:Sequence Deletion; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D015025:Zearalenone / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D005656:Fungal Proteins; D009183:Mycotoxins; D020033:Protein Isoforms; D014157:Transcription Factors; D015025:Zearalenone; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Fusarium graminearum; ZEB2; cAMP dependent signaling; protein kinase A; zearalenone