The COP9 signalosome (CSN) is a highly conserved eukaryotic protein complex which regulates the Cullin-RING family of ubiquitin ligases and carries out a deneddylase activity that resides in subunit 5 (CSN5). Whereas CSN activity is essential for higher eukaryotes development, several unicellular fungi, including the budding yeast S. cerevisiae, can survive without a functional CSN. Nevertheless, the budding yeast CSN is biochemically active and deletion mutants of each of its subunits exhibit deficiency in deneddylation of cullins, although the biological context of this activity is still unknown in this organism. To further characterize CSN function in budding yeast, in this thesis I present a transcriptomic and a proteomic analysis of a S. cerevisiae strain deleted in CSN5, coding for the only canonical subunit of the complex. We discovered that Csn5 is involved in the modulation of the genes controlling aminoacid and lipid metabolism, and especially ergosterol biosynthesis. These alterations in gene expression correlate with the lower ergosterol levels and increased intracellular zinc content which we observed in csn5 null mutant cells. We show that some of these regulatory effects of Csn5, in particular the control of isoprenoid biosynthesis, are conserved through evolution, since similar transcriptomic and/or proteomic effects of csn5 mutation were previously observed in other eukaryotic organisms such as As. nidulans, A. thaliana and D. melanogaster. Our results suggest that the diverged budding yeast Csn is more conserved than was previously thought.
|Titolo:||The COP9 signalosome is involved in the regulation of lipid metabolism and of transition metals uptake in Saccharomyces cerevisiae|
|Data di pubblicazione:||27-feb-2014|
|Appartiene alla tipologia:||07b Tesi di Dottorato (EX-Padis)|