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Dynamics of Cullin-RING Ubiquitin Ligase Network Revealed by Systematic Quantitative Proteomics

Open access
Bennett, Eric J., Rush, John, Gygi, Steven P., Harper, J. Wade·2010·Cell

Abstract

Dynamic reorganization of signaling systems frequently accompany 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 while 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.

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Metadata

Authors
Bennett, E. J., Rush, J., Gygi, S. P., & Harper, J. W.
Venue
Cell
Publisher
Elsevier BV
Published
2010-12
Volume
143
Issue
6
Pages
951-965
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2140252926
Cited by
386
References
6
FWCI
11.93
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Dynamics of Cullin-RING Ubiquitin Ligase Network Revealed by Systematic Quantitative Proteomics. https://app.cochat.ai/papers/10.1016/j.cell.2010.11.017
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Bennett, E. J., Rush, J., Gygi, S. P., & Harper, J. W. (2010). Dynamics of Cullin-RING Ubiquitin Ligase Network Revealed by Systematic Quantitative Proteomics. Cell. https://doi.org/10.1016/j.cell.2010.11.017

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