title: Yap1-dependent oxidative stress response provides a link to riboflavin production in Ashbya gossypii.
abstract: Ashbya gossypii is a natural overproducer of riboflavin. Overproduction of riboflavin can be induced by environmental stress, e.g. nutritional or oxidative stress. The Yap-protein family has a well-documented role in stress response. Particularly, Yap1 has a major role in directing the oxidative stress responses. The A. gossypii YAP-family consists of only three genes in contrast to its closest relative Eremothecium cymbalariae, which has four YAP-homologs. Gene order at Eremothecium YAP-loci is conserved with the reconstructed yeast ancestor. AgYap1p is unique amongst Yap-homologs as it lacks the cysteine-rich domains (CRDs). AgYAP1 expression is inducible and GFP-AgYap1 localizes to the nucleus. Agyap1 mutants displayed higher sensitivity against oxidative stress - H(2)O(2) and menadione - and are strongly reduced in riboflavin production. High levels of cAMP, which also reduce riboflavin production, show a synergistic effect on this sensitivity. AgYAP1 and a chimera of AgYAP1 (with the DNA-binding domain) and ScYAP1 (with the CRDs) can both complement the Scyap1 oxidative stress sensitivity. This suggests that the DNA-binding sites of ScYap1 are conserved in A. gossypii. Expression of AgRIB4, which contains three putative Yap1-binding sites, assayed via a lacZ-reporter gene was strongly reduced in an Agyap1 mutant suggesting a direct involvement of AgYap1 in riboflavin production. Furthermore, our data show that application of H(2)O(2) stress leads to an increase in riboflavin production in a Yap1-dependent manner.
authors: Carlsberg Laboratory, Yeast Biology, Gamle Carlsberg Vej 10, DK-2500 Valby, Copenhagen, Denmark.
authors: Andrea
authors: A
authors: Walther
authors: Jürgen
authors: J
authors: Wendland
mesh_terms: D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D055169:Eremothecium / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012256:Riboflavin / Q000096:biosynthesis*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D012256:Riboflavin