SENP8 limits aberrant neddylation of nedd8 pathway components to promote cullin-RING ubiquitin ligase function Journal Article


Authors: Coleman, K. E.; Békés, M.; Chapman, J. R.; Crist, S. B.; Jones, M. J. K.; Ueberheide, B. M.; Huang, T. T.
Article Title: SENP8 limits aberrant neddylation of nedd8 pathway components to promote cullin-RING ubiquitin ligase function
Abstract: NEDD8 is a ubiquitin-like modifier most well-studied for its role in activating the largest family of ubiquitin E3 ligases, the cullin-RING ligases (CRLs). While many non-cullin neddylation substrates have been proposed over the years, validation of true NEDD8 targets has been challenging, as overexpression of exogenous NEDD8 can trigger NEDD8 conjugation through the ubiquitylation machinery. Here, we developed a deconjugation-resistant form of NEDD8 to stabilize the neddylated form of cullins and other non-cullin substrates. Using this strategy, we identified Ubc12, a NEDD8-specific E2 conjugating enzyme, as a substrate for auto-neddylation. Furthermore, we characterized SENP8/DEN1 as the protease that counteracts Ubc12 autoneddylation, and observed aberrant neddylation of Ubc12 and other NEDD8 conjugation pathway components in SENP8-deficient cells. Importantly, loss of SENP8 function contributes to accumulation of CRL substrates and defective cell cycle progression. Thus, our study highlights the importance of SENP8 in maintaining proper neddylation levels for CRL-dependent proteostasis. © Coleman et al.
Journal Title: eLife
Volume: 6
ISSN: 2050-084X
Publisher: eLife Sciences Publications Ltd.  
Date Published: 2017-05-05
Start Page: e24325
Language: English
DOI: 10.7554/eLife.24325
PROVIDER: scopus
PMCID: PMC5419743
PUBMED: 28475037
DOI/URL:
Notes: Article -- Export Date: 3 July 2017 -- Source: Scopus
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  1. Mathew John Kimble Jones
    11 Jones