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The human COP9 signalosome protects ubiquitin-conjugating enzyme 3 (UBC3/Cdc34) from beta-transducin repeat-containing protein (betaTrCP)-mediated degradation.

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 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00509601
Contributor : Elise Merlo <>
Submitted on : Friday, August 13, 2010 - 3:03:45 PM
Last modification on : Thursday, May 28, 2020 - 5:24:03 PM

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Maria Elena Fernandez-Sanchez, Emmanuel Sechet, Florence Margottin-Goguet, Lars Rogge, Elisabetta Bianchi. The human COP9 signalosome protects ubiquitin-conjugating enzyme 3 (UBC3/Cdc34) from beta-transducin repeat-containing protein (betaTrCP)-mediated degradation.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2010, 285 (23), pp.17390-7. ⟨10.1074/jbc.M109.076661⟩. ⟨pasteur-00509601⟩

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