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Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics.

Cell | Dec 10, 2010

http://www.ncbi.nlm.nih.gov/pubmed/21145461

Dynamic reorganization of signaling systems frequently accompanies pathway perturbations, yet quantitative studies of network remodeling by pathway stimuli are lacking. Here, we report the development of a quantitative proteomics platform centered on multiplex absolute quantification (AQUA) technology to elucidate the architecture of the cullin-RING ubiquitin ligase (CRL) network and to evaluate current models of dynamic CRL remodeling. Current models suggest that CRL complexes are controlled by cycles of CRL deneddylation and CAND1 binding. Contrary to expectations, acute CRL inhibition with MLN4924, an inhibitor of the NEDD8-activating enzyme, does not result in a global reorganization of the CRL network. Examination of CRL complex stoichiometry reveals that, independent of cullin neddylation, a large fraction of cullins are assembled with adaptor modules, whereas only a small fraction are associated with CAND1. These studies suggest an alternative model of CRL dynamicity where the abundance of adaptor modules, rather than cycles of neddylation and CAND1 binding, drives CRL network organization.

Pubmed ID: 21145461 RIS Download

Mesh terms: Cell Line | Cullin Proteins | Cyclopentanes | Protein Processing, Post-Translational | Proteomics | Pyrimidines | Transcription Factors | Ubiquitins

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Associated grants

  • Agency: NIA NIH HHS, Id: R01 AG011085
  • Agency: NIA NIH HHS, Id: R01 AG011085-18
  • Agency: NIGMS NIH HHS, Id: R01 GM054137
  • Agency: NIGMS NIH HHS, Id: R01 GM054137-16
  • Agency: NIGMS NIH HHS, Id: R01 GM070565
  • Agency: NIGMS NIH HHS, Id: R01 GM070565-07

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