the protein kinase tor1 regulates adhesin gene expression in candida albicans基因表达的蛋白激酶tor1调节adhesin白色念珠菌.pdfVIP

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the protein kinase tor1 regulates adhesin gene expression in candida albicans基因表达的蛋白激酶tor1调节adhesin白色念珠菌.pdf

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the protein kinase tor1 regulates adhesin gene expression in candida albicans基因表达的蛋白激酶tor1调节adhesin白色念珠菌

The Protein Kinase Tor1 Regulates Adhesin Gene Expression in Candida albicans 1 1,2,3 1 Robert J. Bastidas , Joseph Heitman , Maria E. Cardenas * 1 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America, 2 Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America, 3 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America Abstract Eukaryotic cell growth is coordinated in response to nutrient availability, growth factors, and environmental stimuli, enabling cell–cell interactions that promote survival. The rapamycin-sensitive Tor1 protein kinase, which is conserved from yeasts to humans, participates in a signaling pathway central to cellular nutrient responses. To gain insight into Tor- mediated processes in human fungal pathogens, we have characterized Tor signaling in Candida albicans. Global transcriptional profiling revealed evolutionarily conserved roles for Tor1 in regulating the expression of genes involved in nitrogen starvation responses and ribosome biogenesis. Interestingly, we found that in C. albicans Tor1 plays a novel role in regulating the expression of several cell wall and hyphal specific genes, including adhesins and their transcriptional repressors Nrg1 and Tup1. In accord with this transcriptional profile, rapamycin induced extensive cellular aggregation in an adhesin-dependent fashion. Moreover, adhesin gene induction and cellular aggregation of rapamycin-treated cells were strongly dependent on the transactivators Bcr1 and Efg1. These