Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

CSN facilitates Cullin-RING ubiquitin ligase function by counteracting autocatalytic adapter instability.

Nature cell biology | Apr 1, 2005

http://www.ncbi.nlm.nih.gov/pubmed/15793566

The COP9 signalosome (CSN) is known to bind cullin-RING ubiquitin ligases (CRLs) and to promote their activity in vivo. The mechanism of this stimulation has remained enigmatic because CSN's intrinsic and associated enzymatic activities paradoxically inhibit CRL activity in vitro. Reconciling this paradox, we show here that Csn5-catalysed cullin (Cul) deneddylation and Ubp12-mediated deubiquitination cooperate in maintaining the stability of labile substrate adapters, thus facilitating CRL function. Various fission-yeast csn and ubp12 deletion mutants have lower levels of the Cul3p adapter Btb3p. This decrease is due to increased autocatalytic, Cul3p-dependent, ubiquitination and the subsequent degradation of Btb3p. The CSN-Ubp12p pathway also maintains the stability of the Cul1p adapter Pop1p, a mechanism required for the efficient destruction of its cognate substrate Rum1p. Emphasizing the physiological importance of this mechanism, we found that the dispensable csn5 and ubp12 genes become essential for viability when adapter recruitment to Cul1p is compromised. Our data suggest that maintenance of adapter stability is a general mechanism of CRL control by the CSN.

Pubmed ID: 15793566 RIS Download

Mesh terms: Adaptor Proteins, Signal Transducing | Catalysis | Cullin Proteins | Endopeptidases | Multiprotein Complexes | Peptide Hydrolases | Proteins | Schizosaccharomyces | Schizosaccharomyces pombe Proteins | Ubiquitin-Protein Ligases

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIEHS NIH HHS, Id: ES00002
  • Agency: NIEHS NIH HHS, Id: ES07155
  • Agency: NIGMS NIH HHS, Id: GM59780
  • Agency: NIGMS NIH HHS, Id: R01 GM059780

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.