Mecanismos de regulación del represor "Nrg1" en "C. albicans"

Resum

The fungus "C. albicans" is normally found as a commensal in the gastrointestinal tract of humans. During long periods of immunosupression caused by new medical therapies, this yeast can produce life-threatening systemic infections with high mortality rates. This oportunistic pathogen is able to activate different developmental programes to rapidly adapt to changing environmental signals. One of the best studied is the ability to switch between different morphological forms, such yeast, pseudohyphae and true hyphae. The yeast-to-hypha transition, triggered by a wide range of environmental cues, is regulated by a network of multiple signalling pathways that control the transcription of a common set of hypha-specific genes (HSGs), many of which encode known virulence factors. During yeast growth, the expression of HSGs is repressed by the DNA-binding protein Nrg1. In this thesis, we have studied the negative regulation of Nrg1 during the yeast-to-hypha transition. Our results have shown that Nrg1 is a phosphoprotein that is degraded at the onset of hyphal growth in a Cbk1/Mob2 and Cdc28/Ccn1-dependent manner. In additions, this degradation is spacially regulated since Nrg1 is accumulated in subapical nuclei whereas is excluded from the apical nucleus of the hypha.