An interaction network of the mammalian COP9 signalosome identifies Dda1 as a core subunit of multiple Cul4-based E3 ligases. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Cell Science Année : 2009

An interaction network of the mammalian COP9 signalosome identifies Dda1 as a core subunit of multiple Cul4-based E3 ligases.

Résumé

The COP9 signalosome (CSN) is an evolutionarily conserved macromolecular complex that interacts with cullin-RING E3 ligases (CRLs) and regulates their activity by hydrolyzing cullin-Nedd8 conjugates. The CSN sequesters inactive CRL4(Ddb2), which rapidly dissociates from the CSN upon DNA damage. Here we systematically define the protein interaction network of the mammalian CSN through mass spectrometric interrogation of the CSN subunits Csn1, Csn3, Csn4, Csn5, Csn6 and Csn7a. Notably, we identified a subset of CRL complexes that stably interact with the CSN and thus might similarly be activated by dissociation from the CSN in response to specific cues. In addition, we detected several new proteins in the CRL-CSN interactome, including Dda1, which we characterized as a chromatin-associated core subunit of multiple CRL4 proteins. Cells depleted of Dda1 spontaneously accumulated double-stranded DNA breaks in a similar way to Cul4A-, Cul4B- or Wdr23-depleted cells, indicating that Dda1 interacts physically and functionally with CRL4 complexes. This analysis identifies new components of the CRL family of E3 ligases and elaborates new connections between the CRL and CSN complexes.

Dates et versions

hal-00389383 , version 1 (28-05-2009)

Identifiants

Citer

Michael Hans Olma, Marcia Roy, Thierry Le Bihan, Izabela Sumara, Sarah Maerki, et al.. An interaction network of the mammalian COP9 signalosome identifies Dda1 as a core subunit of multiple Cul4-based E3 ligases.. Journal of Cell Science, 2009, 122 (Pt 7), pp.1035-44. ⟨10.1242/jcs.043539⟩. ⟨hal-00389383⟩
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