The human COP9 signalosome protects ubiquitin-conjugating enzyme 3 (UBC3/Cdc34) from beta-transducin repeat-containing protein (betaTrCP)-mediated degradation.
The COP9 signalosome (CSN) is an essential multisubunit complex that regulates the activity of cullin-RING ubiquitin ligases by removing the ubiquitin-like peptide NEDD8 from cullins. Here, we demonstrate that the CSN can affect other components of the ubiquitination cascade. Down-regulation of human CSN4 or CSN5 induced proteasome-mediated degradation of the ubiquitin-conjugating enzyme UBC3/Cdc34. UBC3 was targeted for ubiquitination by the cullin-RING ubiquitin ligase SCF(betaTrCP). This interaction required the acidic C-terminal extension of UBC3, which is absent in ubiquitin-conjugating enzymes of the UBCH5 family. Conversely, the UBC3 acidic domain was sufficient to impart sensitivity to SCF(betaTrCP)-mediated ubiquitination to UBCH5 enzymes. Our work indicates that the CSN is necessary to ensure the stability of selected ubiquitin-conjugating enzymes and uncovers a novel pathway of regulation of ubiquitination processes.
Fernandez-Sanchez
Maria Elena
ME
Institut Pasteur, Immunoregulation Unit and CNRS URA1961, 75724 Paris, France.
Sechet
Emmanuel
E
Margottin-Goguet
Florence
F
Rogge
Lars
L
Bianchi
Elisabetta
E
D064173:Anaphase-Promoting Complex-Cyclosome; D000075686:COP9 Signalosome Complex; D002460:Cell Line; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism*; D009841:Oligonucleotides / Q000737:chemistry; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013379:Substrate Specificity; D015293:Transducin / Q000378:metabolism*; D025801:Ubiquitin / Q000737:chemistry; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
D046912:Multiprotein Complexes; D009841:Oligonucleotides; D025801:Ubiquitin; D012313:RNA; C577447:CDC34 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex; D015293:Transducin