Autoinhibitory regulation of SCF-mediated ubiquitination by human cullin 1's C-terminal tail

Yamoah, Kosj; Oashi, Taiji; Sarikas, Antonio; Gazdoiu, Stefan; Osman, Roman; Pan, Zhen‐Qiang

doi:10.1073/pnas.0806155105

Cited by 93 publications

(93 citation statements)

References 26 publications

(29 reference statements)

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“…Like Ltn1, E3s of the CRL family have also been shown to contain flexible regions (22)(23)(24)(25)(26). For example, it is known that the linkage between The CUL1-RBX1 subunits can be highly flexible, regulated by and dependent on posttranslational modification of the complex with the ubiquitin-like protein Nedd8 (22).…”

Section: Discussionmentioning

confidence: 99%

Single-particle EM reveals extensive conformational variability of the Ltn1 E3 ligase

Lyumkis

Doamekpor

Bengtson

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Ltn1 is a 180-kDa E3 ubiquitin ligase that associates with ribosomes and marks certain aberrant, translationally arrested nascent polypeptide chains for proteasomal degradation. In addition to its evolutionarily conserved large size, Ltn1 is characterized by the presence of a conserved N terminus, HEAT/ARM repeats predicted to comprise the majority of the protein, and a C-terminal catalytic RING domain, although the protein's exact structure is unknown. We used numerous single-particle EM strategies to characterize Ltn1's structure based on negative stain and vitreous ice data. Two-dimensional classifications and subsequent 3D reconstructions of electron density maps show that Ltn1 has an elongated form and presents a continuum of conformational states about two flexible hinge regions, whereas its overall architecture is reminiscent of multisubunit cullin-RING ubiquitin ligase complexes. We propose a model of Ltn1 function based on its conformational variability and flexibility that describes how these features may play a role in cotranslational protein quality control.conformational heterogeneity | Ltn1/Listerin | RING E3 ubiquitin ligase | translational surveillance | neurodegenerative disease

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Section: Discussionmentioning

confidence: 99%

Single-particle EM reveals extensive conformational variability of the Ltn1 E3 ligase

Lyumkis

Doamekpor

Bengtson

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, one can think of the un-neddylated state as off or inactive and the neddylated state as on or active. An important unanswered question concerns the extent to which the mobility of the RING domain is important for both the initial ubiquitin transfer step and for processive polyubiquitination, although it is clear that neddylation activates these events (Sidebar D) [61,67,68]. The answer will probably require crystallographic and kinetic analyses of neddylated CRLs bound to charged E2s and substrate.…”

Section: Consequences Of Cullin Neddylation For Crl Activitymentioning

confidence: 99%

Building and remodelling Cullin–RING E3 ubiquitin ligases

2013

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Cullin-RING E3 ubiquitin ligases (CRLs) control a plethora of biological pathways through targeted ubiquitylation of signalling proteins. These modular assemblies use substrate receptor modules to recruit specific targets. Recent efforts have focused on understanding the mechanisms that control the activity state of CRLs through dynamic alterations in CRL architecture. Central to these processes are cycles of cullin neddylation and deneddylation, as well as exchange of substrate receptor modules to re-sculpt the CRL landscape, thereby responding to the cellular requirements to turn over distinct proteins in different contexts. This review is focused on how CRLs are dynamically controlled with an emphasis on how c ullin neddylation cycles are integrated with receptor exchange. Keywords: cullin; ubiquitin; Nedd8; COP9 signalosome; E3 ligase; CAND1 EMBO reports (2013) 14, 1050-1061 published online 15 November 2013; doi:10.1038/embor.2013 See the Glossary for abbreviations used in this article. IntroductionThe proteome is constantly remodelled to suit the needs of the cell, through both synthesis and turnover. Protein turnover is controlled through two main systems: the ubiquitin-proteasome system (UPS) and lysosomal degradation system, including autophagy. Although selective autophagy can provide a means by which to control the abundance of particular organelles and even single proteins, it is best understood as a means to control bulk turnover of cellular components [1]. Conversely, the UPS is a particularly versatile and highly regulated system [2] that allows selective turnover of individual regulatory proteins, even when they are incorporated into higher-order multiprotein assemblies. On the one hand, the entire population of a given protein targeted by the UPS might be subject to rapid tagging with ubiquitin and degradation by the proteasome. On the other hand, the UPS might control the degradation of only a small pool of a particular target protein, for example the population of a protein that has been phosphorylated by an upstream pathway. Thus, the UPS functions in space and time to sculpt the proteome and to control the abundance of active or inactive forms of signalling complexes and cellular machines. As illustrated in this Review, the UPS machinery that controls turnover of a wide swathe of the p roteome is itself dynamically regulated through many mechanisms.The tagging of proteins with particular types of ubiquitin chains serves to mark them for proteasomal degradation. This process occurs through an E1 (ubiquitin-activating enzyme)-E2 (ubiquitinconjugating enzyme)-E3 (ubiquitin ligase) cascade [3][4][5][6][7]. E3 plays a central role in substrate targeting by binding directly to the substrate and presenting target lysine residues to receive ubiquitin from the E2, in the case of RING E3s, or from a ubiquitin-charged cysteine residue in HECT and RBR E3s [6,[8][9][10]. Cullin-RING E3 ubiquitin ligases (CRLs), which were first discovered almost two decades ago [11][12][13], are a superfamily of RING E3...

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“…Since Cul7 is the only other known cullin that binds F-box proteins ( Fig. 1), [34][35][36] and FBG1 bound Cul1 poorly, we tested whether FBG1 binds Cul7. As seen in Figure 2 co-expression of any FBG protein, especially FBG1 and FBG3, with Cul7 increases the steady-state level of Cul7.…”

Section: Fbg1 Interacts With Different Cullinmentioning

confidence: 99%

FBG1 is a promiscuous ubiquitin ligase that sequesters APC2 and causes S-phase arrest

Wen¹,

Kim

Fuentes

et al. 2010

Cell Cycle

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Autoinhibitory regulation of SCF-mediated ubiquitination by human cullin 1's C-terminal tail

Cited by 93 publications

References 26 publications

Single-particle EM reveals extensive conformational variability of the Ltn1 E3 ligase

Single-particle EM reveals extensive conformational variability of the Ltn1 E3 ligase

Building and remodelling Cullin–RING E3 ubiquitin ligases

FBG1 is a promiscuous ubiquitin ligase that sequesters APC2 and causes S-phase arrest

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