title: The COP9 signalosome is involved in the regulation of lipid metabolism and of transition metals uptake in Saccharomyces cerevisiae.
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.
authors.affiliation: Istituto Pasteur - Fondazione Cenci Bolognetti, Department of Biology and Biotechnology 'C. Darwin', Sapienza University of Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Licursi
authors.forename: Chiara
authors.initials: C
authors.lastname: Salvi
authors.forename: Virginia
authors.initials: V
authors.lastname: De Cesare
authors.forename: Teresa
authors.initials: T
authors.lastname: Rinaldi
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mattei
authors.forename: Claudia
authors.initials: C
authors.lastname: Fabbri
authors.forename: Giovanna
authors.initials: G
authors.lastname: Serino
authors.forename: Laylan
authors.initials: L
authors.lastname: Bramasole
authors.forename: Jacob Z
authors.initials: JZ
authors.lastname: Zimbler
authors.forename: Elah
authors.initials: E
authors.lastname: Pick
authors.forename: Brett M
authors.initials: BM
authors.lastname: Barnes
authors.forename: Martin
authors.initials: M
authors.lastname: Bard
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Negri
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D000075686:COP9 Signalosome Complex; D002849:Chromatography, Gas; D002853:Chromatography, Liquid; D044842:Cullin Proteins / Q000378:metabolism*; D004875:Ergosterol / Q000378:metabolism; D020869:Gene Expression Profiling; D050356:Lipid Metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010447:Peptide Hydrolases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D028561:Transition Elements / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
chemical_list: D015415:Biomarkers; C100988:Cdc53 protein, S cerevisiae; D044842:Cullin Proteins; D046912:Multiprotein Complexes; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D028561:Transition Elements; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex; D008666:Metalloendopeptidases; C468276:Rri1 protein, S cerevisiae; D015032:Zinc; D004875:Ergosterol
keywords: COP9 signalosome; ergosterol biosynthesis; lipid metabolism; neddylation; zinc uptake