title: Yap5 is an iron-responsive transcriptional activator that regulates vacuolar iron storage in yeast.
abstract: The transporter Ccc1 imports iron into the vacuole, which is the major site of iron storage in fungi and plants. CCC1 mRNA is destabilized under low-iron conditions by the binding of Cth1 and Cth2 to the 3' untranslated region (S. Puig, E. Askeland, and D. J. Thiele, Cell 120:99-110, 2005). Here, we show that the transcription of CCC1 is stimulated by iron through a Yap consensus site in the CCC1 promoter. We identified YAP5 as being the iron-sensitive transcription factor and show that a yap5Delta strain is sensitive to high iron. Green fluorescent protein-tagged Yap5 is localized to the nucleus and occupies the CCC1 promoter independent of the iron concentration. Yap5 contains two cysteine-rich domains, and the mutation of the cysteines to alanines in each of the domains affects the transcription of CCC1 but not DNA binding. The fusion of the Yap5 cysteine-containing domains to a GAL4 DNA binding domain results in iron-sensitive GAL1-lacZ expression. Iron affects the sulfhydryl status of Yap5, which is indicative of the generation of intramolecular disulfide bonds. These results show that Yap5 is an iron-sensing transcription factor and that iron regulates transcriptional activation.
authors: Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
authors: Liangtao
authors: L
authors: Li
authors: Dustin
authors: D
authors: Bagley
authors: Diane M
authors: DM
authors: Ward
authors: Jerry
authors: J
authors: Kaplan
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D027682:Cation Transport Proteins; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003545:Cysteine; D000939:Epitopes; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D017930:Genes, Reporter; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D007763:Lac Operon; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C089360:CCC1 protein, S cerevisiae; D027682:Cation Transport Proteins; D000939:Epitopes; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C526591:Yap5 protein, S cerevisiae; D007501:Iron; D003545:Cysteine