NEDD8 recruits E2-ubiquitin to SCF E3 ligase

Kawakami, Takayuki; Chiba, Tomoki; Suzuki, Toshiaki; Iwaï, Kazuhiro; Yamanaka, Koji; Minato, Nagahiro; Suzuki, Hiroshi; Shimbara, Naoki; Hidaka, Yuko; Osaka, Fumio; Omata, Masao; Tanaka, Keiji

doi:10.1093/emboj/20.15.4003

Cited by 289 publications

(249 citation statements)

References 41 publications

(97 reference statements)

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“…Neddylation promotes E2 recruitment in Cullins 49,50 . We investigated whether neddylation had any effects on Smurf1 interaction with ubiquitin E2.…”

Section: Articlementioning

confidence: 99%

The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis

et al. 2014

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Neddylation, the covalent attachment of ubiquitin-like protein Nedd8, of the Cullin-RING E3 ligase family regulates their ubiquitylation activity. However, regulation of HECT ligases by neddylation has not been reported to date. Here we show that the C2-WW-HECT ligase Smurf1 is activated by neddylation. Smurf1 physically interacts with Nedd8 and Ubc12, forms a Nedd8-thioester intermediate, and then catalyses its own neddylation on multiple lysine residues. Intriguingly, this autoneddylation needs an active site at C426 in the HECT N-lobe. Neddylation of Smurf1 potently enhances ubiquitin E2 recruitment and augments the ubiquitin ligase activity of Smurf1. The regulatory role of neddylation is conserved in human Smurf1 and yeast Rsp5. Furthermore, in human colorectal cancers, the elevated expression of Smurf1, Nedd8, NAE1 and Ubc12 correlates with cancer progression and poor prognosis. These findings provide evidence that neddylation is important in HECT ubiquitin ligase activation and shed new light on the tumour-promoting role of Smurf1.

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“…Neddylation promotes E2 recruitment in Cullins 49,50 . We investigated whether neddylation had any effects on Smurf1 interaction with ubiquitin E2.…”

Section: Articlementioning

confidence: 99%

The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis

et al. 2014

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“…Using in vitro systems, several studies have shown that Nedd8 activated the SCF-mediated ubiquitination of IkBa (Read et al, 2000;Kawakami et al, 2001) or p27 Morimoto et al, 2000) through its conjugation to CUL1. Subsequently, it was observed that neddylation of CUL2 was also required for efficient ubiquitination of HIF-a by the pVHL E3 ligase (Ohh et al, 2002).…”

Section: Role For Nedd8 In Assisting the Landing And Positioning Of Ementioning

confidence: 99%

“…Read et al (2000) showed that neddylation did not affect the assembly of the SCF bTrCP complex, nor did it alter the binding of this E3 to IkBa. Furthermore, highly purified components were used exclusively to show that SCF b-TrCP was more active than SCF b-TrCP containing CUL1 K720R in the ubiquitination of IkBa (Kawakami et al, 2001). It is, therefore, unlikely that the observed activation is due to an additional factor.…”

Section: Role For Nedd8 In Assisting the Landing And Positioning Of Ementioning

confidence: 99%

Nedd8 on cullin: building an expressway to protein destruction

et al. 2004

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This review summarizes recent advances concerning the Nedd8 regulatory pathway in four areas. One, substantial progress has been made in delineating the role of cullin family proteins, the only known substrates of the Nedd8 modification system. Cullins are molecular scaffolds responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. Two, a large body of work has helped elucidate the molecular details underlying the Nedd8 modification reaction, which results in covalent conjugation of a Nedd8 moiety onto a conserved cullin lysine residue. Three, studies using a variety of genetic model systems have established an essential role for Nedd8 in cell cycle control and in embryogenesis by upregulating the activities of cullin-based E3 ligases. In vitro experiments have revealed a direct role for Nedd8 in activating ubiquitination. Construction of a model of the ROC1/ Rbx1-CUL1-Nedd8 structure suggests a mechanism by which the cullin-linked Nedd8 may assist the neighboring ROC1/Rbx1 in landing and positioning the E2 conjugating enzyme for the ubiquitin transfer reaction. Finally, increasing evidence indicates that removal of Nedd8 from its cullin targets, by the action of COP9 Signalosome and possibly other proteases, plays a significant role in the regulation of cullin-mediated proteolysis.

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“…How this occurs is not clear because CUL1 modification affects neither assembly nor stability of the Review SCF. However, it has been suggested that NEDD8/RUB1 modification might enhance the affinity of the cullin for the ubiquitin E2 [33,34]. Thus, one function of the modification might be to recruit the E2 to the SCF complex ( Figure 1).…”

Section: Auxin Modulates Gene Transcriptionmentioning

confidence: 99%

Auxin signaling and regulated protein degradation

Dharmasiri

Estelle

2004

Trends in Plant Science

226

137

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Auxin regulates many aspects of plant growth and development. Auxin is known to regulate gene expression through degradation of the AUX/IAA proteins, short-lived nuclear proteins that regulate gene transcription. The AUX/IAA proteins are degraded through the action of a ubiquitin protein ligase called SCF TIR1 . Auxin promotes the interaction between AUX/IAA proteins and SCF TIR1 in a soluble extract, suggesting that the auxin receptor is a soluble factor. These studies also indicate that the auxin-induced AUX/IAA -SCF TIR1 interaction does not depend on phosphorylation or hydroxylation of AUX/IAA proteins. Although the mechanism of auxin-induced AUX/IAA -SCF TIR1 interaction is not yet clear, auxin might induce a modification in TIR1, AUX/IAA proteins or an adaptor protein that is required for the interaction.Auxin plays a pivotal role in many processes throughout the plant life cycle. These include embryogenesis, lateral root development, vascular differentiation, apical dominance, tropic responses and flower development. Auxin was first discovered decades ago [1]. In spite of the tremendous amount of information that has accumulated since then, the auxin signaling pathways have not been fully elucidated. Nevertheless, through the combined application of genetic, molecular and biochemical methods, we are beginning to understand some aspects of auxin action. In this article, we discuss recent developments in the study of auxin signaling, particularly focusing on auxin-regulated transcription.

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NEDD8 recruits E2-ubiquitin to SCF E3 ligase

Cited by 289 publications

References 41 publications

The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis

The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis

Nedd8 on cullin: building an expressway to protein destruction

Auxin signaling and regulated protein degradation

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