| Título: | Roles of zinc cluster protein transcription factors in conferring drug resistance in Saccharomyces cerevisiae and Candida albicans |
| Autores: | MacPherson, Sarah A. |
| Fecha: | 2005 |
| Publicador: | McGill University - MCGILL |
| Fuente: |
 |
| Tipo: | Electronic Thesis or Dissertation |
| Tema: | Biology, Microbiology. |
| Descripción: | Multi-drug or pleiotropic drug resistance (PDR) is a universally acquired mechanism that is evolutionarily conserved. Saccharomyces cerevisiae serves as an excellent model organism for studying this phenomenon in pathogenic fungi, such as Candida albicans. In yeast, PDR is most often mediated by the overexpression of membrane-spanning transporter proteins that act as drug efflux pumps. Their expression is controlled by an intricate network of transcription factors, including many members of the Gal4p superfamily of zinc cluster proteins. Pdr1p, Pdr3p, Pdr8p, Stb5p, Yrm1p, and Yrr1p are all transcriptional activators that make up the PDR network. Upc2p and Ecm22p are two other transcription factors in this family that contribute to drug resistance by effecting changes in the ergosterol biosynthetic pathway. Unlike S. cerevisiae, transcription factors contributing to PDR in C. albicans are virtually unknown. Using comparative genomics, we characterized a homologue of Upc2p in C. albicans. We show that overexpression of C. albicans UPC2 confers resistance to several drugs, and its gene product regulates transcription of several ergosterol genes. In addition, we recently identified a novel zinc cluster protein in S. cerevisiae, Rdr1p, which acts as a trancriptional repressor of multi-drug resistance genes. We demonstrate that Rdr1p forms homodimers in vivo, and does not heterodimerize with any of the other transcription factors tested. These results favour a model in which Rdr1p negatively regulates transcription by competing for binding with other factors to elements within the promoters of target genes. Together, these data imply that this family's role in drug resistance is conserved, and that our knowledge of zinc cluster proteins in budding yeast can be applied to pathogenic fungal species. |
| Idioma: | en |
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