2017
DOI: 10.7554/elife.24325
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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-cu… Show more

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Cited by 37 publications
(45 citation statements)
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“…We also copurified hyper-neddylated forms of Cul2 and Cul3 from NEDP1 KO cells ( Fig 1C). These results support previous work that has concluded that NEDP1 cleaves NEDD8 from the enzymes involved in cullin neddylation, as well as from erroneously neddylated cullins (Mergner et al, 2015;Coleman et al, 2017). These results support previous work that has concluded that NEDP1 cleaves NEDD8 from the enzymes involved in cullin neddylation, as well as from erroneously neddylated cullins (Mergner et al, 2015;Coleman et al, 2017).…”
Section: Resultssupporting
confidence: 91%
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“…We also copurified hyper-neddylated forms of Cul2 and Cul3 from NEDP1 KO cells ( Fig 1C). These results support previous work that has concluded that NEDP1 cleaves NEDD8 from the enzymes involved in cullin neddylation, as well as from erroneously neddylated cullins (Mergner et al, 2015;Coleman et al, 2017). These results support previous work that has concluded that NEDP1 cleaves NEDD8 from the enzymes involved in cullin neddylation, as well as from erroneously neddylated cullins (Mergner et al, 2015;Coleman et al, 2017).…”
Section: Resultssupporting
confidence: 91%
“…The physiological substrates of NEDP1, however, remain largely unknown. Furthermore, poly-NEDD8 chains have been identified by mass spectrometry, and as cullins are only mono-neddylated, this finding strongly suggests that NEDD8 fulfils other roles Leidecker et al, 2012;Coleman et al, 2017). Similarly, the overall cellular neddylation pattern of proteins changes when cells are exposed to oxidative stress (Leidecker et al, 2012).…”
Section: Introductionmentioning
confidence: 97%
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