Fission yeast COP9/signalosome suppresses cullin activity through recruitment of the deubiquitylating enzyme Ubp12p.
The COP9/signalosome (CSN) is known to remove the stimulatory NEDD8 modification from cullins. The activity of the fission yeast cullins Pcu1p and Pcu3p is dramatically stimulated when retrieved from csn mutants but inhibited by purified CSN. This inhibition is independent of cullin deneddylation but mediated by the CSN-associated deubiquitylating enzyme Ubp12p, which forms a complex with Pcu3p in a CSN-dependent manner. In ubp12 mutants, as in csn mutants, Pcu3p activity is stimulated. CSN is required for efficient targeting of Ubp12p to the nucleus, where both cullins reside. Finally, the CSN/Ubp12p pathway maintains the stability of the Pcu1p-associated substrate-specific adaptor protein Pop1p. We propose that CSN/Ubp12p-mediated deubiquitylation creates an environment for the safe de novo assembly of cullin complexes by counteracting the autocatalytic destruction of adaptor proteins.
Zhou
Chunshui
C
Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Wee
Susan
S
Rhee
Edward
E
Naumann
Michael
M
Dubiel
Wolfgang
W
Wolf
Dieter A
DA
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000075686:COP9 Signalosome Complex; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D044842:Cullin Proteins; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes; D009154:Mutation / Q000235:genetics; D010447:Peptide Hydrolases; D011485:Protein Binding / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D025801:Ubiquitin / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D046912:Multiprotein Complexes; D011506:Proteins; D012261:Ribonucleoproteins; D029702:Schizosaccharomyces pombe Proteins; D025801:Ubiquitin; C490348:pop1 protein, S pombe; D010450:Endopeptidases; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex; C474614:Ubp12 protein, S pombe