title: Mutations in the pho2 (bas2) transcription factor that differentially affect activation with its partner proteins bas1, pho4, and swi5.
abstract: The yeast PHO2 gene encodes a homeodomain protein that exemplifies combinatorial control in transcriptional activation. Pho2 alone binds DNA in vitro with low affinity, but in vivo it activates transcription with at least three disparate DNA-binding proteins: the zinc finger protein Swi5, the helix-loop-helix factor Pho4, and Bas1, an myb-like activator. Pho2 + Swi5 activates HO, Pho2 + Pho4 activates PHO5, and Pho2 + Bas1 activates genes in the purine and histidine biosynthesis pathways. We have conducted a genetic screen and identified 23 single amino acid substitutions in Pho2 that differentially affect its ability to activate its specific target genes. Analysis of the mutations suggests that the central portion of Pho2 serves as protein-protein interactive surface, with a requirement for distinct amino acids for each partner protein.
authors.affiliation: Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
authors.forename: Leena T
authors.initials: LT
authors.lastname: Bhoite
authors.forename: Jason M
authors.initials: JM
authors.lastname: Allen
authors.forename: Emily
authors.initials: E
authors.lastname: Garcia
authors.forename: Lance R
authors.initials: LR
authors.lastname: Thomas
authors.forename: I David
authors.initials: ID
authors.lastname: Gregory
authors.forename: Warren P
authors.initials: WP
authors.lastname: Voth
authors.forename: Kristen
authors.initials: K
authors.lastname: Whelihan
authors.forename: Ronda J
authors.initials: RJ
authors.lastname: Rolfes
authors.forename: David J
authors.initials: DJ
authors.lastname: Stillman
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism*; D005822:Genetic Vectors; D018398:Homeodomain Proteins; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D017354:Point Mutation; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D018398:Homeodomain Proteins; C051611:PHO2 protein, S cerevisiae; C060292:PHO4 protein, S cerevisiae; D011994:Recombinant Proteins; C080218:SWI5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors