Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and -independent mechanisms.
The signalosome is implicated in regulating cullin-dependent ubiquitin ligases. We find that two signalosome subunits, Csn1 and Csn2, are required to regulate ribonucleotide reductase (RNR) through the degradation of a small protein, Spd1, that acts to anchor the small RNR subunit in the nucleus. Spd1 destruction correlates with the nuclear export of the small RNR subunit, which, in turn, correlates with a requirement for RNR in replication and repair. Spd1 degradation is promoted by two separate CSN-dependent mechanisms. During unperturbed S phase, Spd1 degradation is independent of checkpoint proteins. In irradiated G2 cells, Spd1 degradation requires the DNA damage checkpoint. The signalosome copurifies with Pcu4 (cullin 4). Pcu4, Csn1, and Csn2 promote the degradation of Spd1, identifying a new function for the signalosome as a regulator of Pcu4-containing E3 ubiquitin ligase.
Liu
Cong
C
Genome Damage and Stability Centre, University of Sussex, Falmer, BN1 9RQ, UK.
Powell
Kelly A
KA
Mundt
Kirsten
K
Wu
LeJung
L
Carr
Antony M
AM
Caspari
Thomas
T
D000075686:COP9 Signalosome Complex; D018797:Cell Cycle Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D018816:Genes, cdc; D046912:Multiprotein Complexes; D010447:Peptide Hydrolases; D011506:Proteins / Q000378:metabolism*; D012264:Ribonucleotide Reductases / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D046912:Multiprotein Complexes; D011506:Proteins; D029702:Schizosaccharomyces pombe Proteins; C102445:Spd1 protein, S pombe; D012264:Ribonucleotide Reductases; C080927:SUC22 protein, S pombe; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex