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Title: Phospho-regulation of the Candida albicans hyphal repressor Nrg1 by the action of multiple kinases
Author: Alaalm , Leenah M.
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2012
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The ability of C. albicans to reversibly switch between different morphological forms contributes to its virulence as a fungal pathogen. In this research, the molecular mechanisms that control hyphal development in C. albicans were of particular interest because this phenomenon plays an essential role in this pathogen's virulence and pathogenicity. The morphological switching in C. albicans is triggered by various environmental cues. Signal transduction pathways are the primary mechanisms by which cells sense changes in their environment and initiate an adaptive response. In C. albicans, hyphal development is subjected to both positive and negative regulation. The negative regulation of hyphal development is mediated by a repression pathway that involves the recruitment of the repressor Tup1 to the DNA. This study examined the negative regulation of hyphal induction by a particular DNA-binding protein, namely, the negative regulator of filamentous growth (Nrg1). In particular, this study focused on the role of C. albicans Nrg1 in regulating hypha I growth. In C. albicans, cells that lack Nrg1 are characterised by a constitutive filamentous phenotype in both liquid and solid media. The inactivation of Nrg1 causes filamentous growth because the expression of hypha I-specific genes (HSGs) is de-repressed if Nrg1 fails to bind to the promotes of these HSGs. In this study, the mechanisms by which the repression of Nrg1 is relieved during the morphological transition from yeast to hyphae were investigated. In particular, this study assessed the possible phospho-regulation of Nrg1 by three kinases: the cyclin-dependent kinase Cdc28, the cell wall biosynthesis kinase Cbk1 and its upstream activating kinase Kic1. Three Cbk1 consensus target sites in Nrg1, namely, S200, T251 and T281, were identified in this study. Two of these Cbk1 phosphorylation sites, T251 and H 8t, are located in the DNA-binding domain of Nrg1 , specifically at the end of each zinc finger of this protein.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available