Conservation of the COP9/signalosome in budding yeast

Abstract

Background: The COP9/signalosome (CSN), a multiprotein complex consisting of eight subunits, is implicated in a wide variety of regulatory processes including cell cycle control, signal transduction, transcriptional activation, and plant photomorphogenesis. Some of these functions have been linked to CSN-associated enzymes, including kinases and an activity that removes the ubiquitin-like protein NEDD8/Rub1p from the cullin subunit of E3 ligases. CSN is highly conserved across species from fission yeast to humans, but sequence comparison has failed to identify the complex in budding yeast, except for a putative CSN5 subunit called Rri1p. Results: We show that disruption of four budding yeast genes, PCI8 and three previously uncharacterized ORFs, which encode proteins interacting with Rrr1p/Csn5p, each results in the accumulation of the cullin Cdc53p exclusively in the Rub1p-modified state. This phenotype, which resembles that of fission yeast csn mutants, is due to a biochemical defect in deneddylation that is complemented by wild-type cell lysate and by purified human CSN in vitro. Although three of the four genes encode proteins with PCI domains conserved in metazoan CSN proteins, their disruption does not confer the DNA damage sensitivity described in some fission yeast csn mutants. Conclusions: Our studies present unexpected evidence for the conservation of a functional homologue of the metazoan CSN, which mediates control of cullin neddylation in budding yeast.

COP9 signalosome components play a role in the mating pheromone response of S. cerevisiae

“…Deletions of csn5, csn9, csn10, pci8/csn11 or csi1 bring about accumulation of Rub1-modified Cdc53/cullin, confirming that the CSN partakes in cullin modification in budding yeast ( Figure 3A). While this paper was under review, these results were independently confirmed (Wee et al, 2002), and evidence that Csn5/Rri1 is the catalytic subunit was demonstrated (Cope et al, 2002). Interestingly, Cdc53 modification is insignificantly altered in Δcsn12, which promotes complex disassociation, indicating that integrity of the entire complex is not essential for this hydrolase activity ( Figure 3A).…”

COP9 signalosome function in the DDR

“…Why this depends on CSN1 and CSN2 but not on CSN3 and CSN4 is still not clear. In contrast to S. pombe, there is no delay in S phase in the budding yeast S. cerevisiae after CSN subunit deletion nor are mutants hypersensitive to UV [4]. However, homologs of CSN1 or CSN2 are not clearly identifiable in these species [4] and levels of overall sequence identity between subunits from budding yeast and those from other organisms are extremely low [27].…”

The COP9 signalosome is an essential regulator of development in the filamentous fungus Aspergillus nidulans

“…2B). The putative yeast CSN5 counterpart, Rri1p (Wee et al, 2002), exhibits only 20% identities (not shown). The gene was named csnE csnD:gfp wild-type Fig.…”