title: The evolutionary rewiring of the ribosomal protein transcription pathway modifies the interaction of transcription factor heteromer Ifh1-Fhl1 (interacts with forkhead 1-forkhead-like 1) with the DNA-binding specificity element.
abstract: The genes encoding the ribosomal proteins of fungi form a regulon whose expression is enhanced under good growth conditions and down-regulated under starvation conditions. The fungal pathogen Candida albicans contains an evolutionarily ancient control circuit for this regulon where a heteromer made up of the transcription regulators Ifh1 (interacts with Forkhead 1) and Fhl1 (Forkhead-like 1) is targeted to the ribosomal protein genes by the DNA binding factor Tbf1. In the more recently evolved circuit in the model yeast Saccharomyces cerevisiae (Sc), the generalist repressor-activator protein Rap1 now directs the Ifh1-Fhl1 module to the ribosomal protein genes. Even though overall sequence similarity is low for the respective Fhl1 and Ifh1 subunits, in both species, the Ifh1 protein links to the Forkhead-associated domain of Fhl1 through its FHB domain. Intriguingly, correlated with the transition to the Rap1-regulated circuit, the Sc-Ifh1 contains a Rap1 binding domain that is not present in the C. albicans protein. Because no extensive common sequences are found in Tbf1 and Rap1, it appears that these targeting proteins must connect to the Ifh1-Fhl1 module in distinct ways. Two-hybrid and co-immunoprecipitation analysis has been used to show that in C. albicans Tbf1 is linked to the heterodimer through direct association with Fhl1. By contrast, in S. cerevisiae, the linkage of the heteromer to Rap1 occurs through Ifh1. Thus, in the ascomycetes, the Ifh1-Fhl1 heterodimer has reconfigured its protein associations to remain connected to the ribosomal protein regulon despite rewiring of the targeting transcription factor from Tbf1 to Rap1.
authors.affiliation: Centre for Structural and Functional Genomics, Biology Department, Concordia University, Montréal, Québec H4B 1R6, Canada.
authors.forename: Jaideep
authors.initials: J
authors.lastname: Mallick
authors.forename: Malcolm
authors.initials: M
authors.lastname: Whiteway
mesh_terms: D000595:Amino Acid Sequence; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D019143:Evolution, Molecular; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D047468:Immunoprecipitation; D050296:Microbial Viability; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D004268:DNA-Binding Proteins; C495776:FHL1 protein, S cerevisiae; D051858:Forkhead Transcription Factors; C094046:IFH1 protein, S cerevisiae; C440829:RAP1 protein, S cerevisiae; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; C079376:TBF1 protein, S cerevisiae; D034501:Telomere-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors
keywords: Candida albicans; Protein Evolution; Protein-Protein Interactions; Rewiring; Transcription Regulation; Yeast Transcription