The Human COP9 Signalosome Protects Ubiquitin-conjugating Enzyme 3 (UBC3/Cdc34) from β-Transducin Repeat-containing Protein (βTrCP)-mediated Degradation |
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Authors: | Maria Elena Fernandez-Sanchez Emmanuel Sechet Florence Margottin-Goguet Lars Rogge Elisabetta Bianchi |
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Institution: | From the ‡Institut Pasteur, Immunoregulation Unit and CNRS URA1961, 75724 Paris and ;the §Institut Cochin, Université Paris Descartes, CNRS UMR 8104, and ;¶INSERM, U1016, 75014 Paris, France |
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Abstract: | 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 SCFβTrCP. 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 SCFβTrCP-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. |
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Keywords: | Proteases/Ubiquitin Proteases/Ubiquitination Protein/Degradation Ubiquitin-conjugating Enzyme (Ubc) Ubiquitination Cdc34 COP9 Signalosome UBC3 betaTrCP |
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