The COP9 signalosome is involved in the regulation of lipid metabolism and of transition metals uptake in Saccharomyces cerevisiae

Valerio Licursi, Chiara Salvi, Virginia De Cesare, Teresa Rinaldi, Benedetta Mattei, Claudia Fabbri, Giovanna Serino, Laylan Bramasole, Jacob Z. Zimbler, Elah Pick, Brett M. Barnes, Martin Bard, Rodolfo Negri

Research output: Contribution to journalArticlepeer-review

Abstract

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 the development of higher eukaryotes, several unicellular fungi including the budding yeast Saccharomyces 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 cullins deneddylation, although the biological context of this activity is still unknown in this organism. To further characterize CSN function in budding yeast, we present here a transcriptomic and proteomic analysis of a S. Cerevisiae strain deleted in the CSN5/RRI1 gene (hereafter referred to as CSN5), coding for the only canonical subunit of the complex. We show that Csn5 is involved in modulation of the genes controlling amino acid 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 Aspergillus nidulans, Arabidopsis thaliana and Drosophila melanogaster. Our results suggest that the diverged budding yeast CSN is more conserved than was previously thought.

Original languageEnglish
Pages (from-to)175-190
Number of pages16
JournalFEBS Journal
Volume281
Issue number1
DOIs
StatePublished - Jan 2014

Keywords

  • COP9 signalosome
  • ergosterol biosynthesis
  • lipid metabolism
  • neddylation
  • zinc uptake

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology

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