The Zinc Finger of the CSN-Associated Deubiquitinating Enzyme USP15 Is Essential to Rescue the E3 Ligase Rbx1

Hetfeld, Bettina K. J.; Helfrich, Annett; Kapelari, Barbara; Scheel, Hartmut; Hofmann, Kay; Guterman, Adi; Glickman, Michael S.; Schade, Rüdiger; Kloetzel, Peter‐Michael; Dubiel, Wolfgang

doi:10.1016/j.cub.2005.05.059

Cited by 133 publications

(169 citation statements)

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“…Migrations of complexes that cross-react with the anti-CSN6 antibody were not affected by apoptosis. This was also true for the associated enzyme USP15, which co-sedimented with the CSN into fraction 8 (data not shown) and partially dissociated during glycerol gradient centrifugation as published before [31]. As seen in Fig.…”

Section: Caspase Cleavage Of Csn6 Is Accompanied By Cleavage Of Rbx1supporting

confidence: 80%

“…Aliquots were subjected to SDS-PAGE and Western blotting. The following antibodies were used in this study: anti-CSN1, anti-CSN4, anti-CSN6 and anti-CSN8 antibodies (Biomol), anti-CSN2, anti-CSN3 and anti-CSN7 antibodies [29,30], monoclonal anti-CSN5 antibody (supplied by B. Christy), anti-ubiquitin antibody (FK2, Biomol), anti-USP15 antibody [31], anti-Rbx1 antibody (Rockland), anti-Nedd8 antibody (a gift from C.…”

Section: Cell Culture and Materialsmentioning

confidence: 99%

“…In addition, the CSN is associated with a deubiquitinating enzyme called USP15 and with kinases such as CK2 and PKD [30,31,39].…”

Section: Caspase Cleavage Of Csn6 Is Accompanied By Cleavage Of Rbx1mentioning

confidence: 99%

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The COP9 signalosome-mediated deneddylation is stimulated by caspases during apoptosis

et al. 2007

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In concert with the ubiquitin (Ub) proteasome system (UPS) the COP9 signalosome (CSN) controls the stability of cellular regulators. The CSN interacts with cullin-RING Ub ligases (CRLs) consisting of a specific cullin, a RING protein as Rbx1 and substrate recognition proteins. The Ub-like protein Nedd8 is covalently linked to cullins and removed by the CSN-mediated deneddylation. Cycles of neddylation and deneddylation regulate CRLs. Apoptotic stimuli cause caspase-dependent modifications of the UPS.

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Section: Caspase Cleavage Of Csn6 Is Accompanied By Cleavage Of Rbx1supporting

confidence: 80%

Section: Cell Culture and Materialsmentioning

confidence: 99%

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The COP9 signalosome-mediated deneddylation is stimulated by caspases during apoptosis

et al. 2007

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“…Multiple studies from a range of organisms have shown that CSN interacts with Cullin-RING E3s and that proper E3 function is dependent on CSN and more specifically on CSN5-mediated deneddylation Schwechheimer et al, 2001;Schwechheimer, 2004). Some recent studies suggest that deneddylation is required for E3 subunit stability or E3 complex assembly (Hetfeld et al, 2005;Wee et al, 2005;Wu et al, 2005;Bornstein et al, 2006). Furthermore, it has been proposed that CSN is part of a proteasome-related complex (Peng et al, 2001(Peng et al, , 2003.…”

Section: Introductionmentioning

confidence: 99%

Characterization of theVIER F-BOX PROTEINEGenes fromArabidopsisReveals Their Importance for Plant Growth and Development

et al. 2007

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E3 ubiquitin ligases (E3s) target proteins for degradation by the 26S proteasome. In SKP1/CDC53/F-box protein–type E3s, substrate specificity is conferred by the interchangeable F-box protein subunit. The vast majority of the 694 F-box proteins encoded by the Arabidopsis thaliana genome remain to be understood. We characterize the VIER F-BOX PROTEINE (VFB; German for FOUR F-BOX PROTEINS) genes from Arabidopsis that belong to subfamily C of the Arabidopsis F-box protein superfamily. This subfamily also includes the F-box proteins TRANSPORT INHIBITOR RESPONSE1 (TIR1)/AUXIN SIGNALING F-BOX (AFB) proteins and EIN3 BINDING F-BOX proteins, which regulate auxin and ethylene responses, respectively. We show that loss of VFB function causes delayed plant growth and reduced lateral root formation. We find that the expression of a number of auxin-responsive genes and the activity of DR5:β-glucuronidase, a reporter for auxin reponse, are reduced in the vfb mutants. This finding correlates with an increase in the abundance of an AUXIN/INDOLE-3-ACETIC ACID repressor. However, we also find that auxin responses are not affected in the vfb mutants and that a representative VFB family member, VFB2, cannot functionally complement the tir1-1 mutant. We therefore exclude the possibility that VFBs are functional orthologs of TIR1/AFB proteins.

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“…In the subsequent years, the highly conserved protein complex was also found in fungi (3,4), Caenorhabditis elegans (5), Drosophila melanogaster (6), and mammals (7,8). The most studied function of the CSN complex in eukaryotes is the regulation of protein degradation through two pathways, deneddylation (9)(10)(11) and deubiquitination (12,13). In the deneddylation pathway, the CSN complex can influence the cullin-RING ligase activity by removing Nedd8, a ubiquitin-like protein, from a cullin (9,14).…”

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confidence: 99%

Crystal structure and versatile functional roles of the COP9 signalosome subunit 1

Lee

et al. 2013

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

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The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) plays key roles in many biological processes, such as repression of photomorphogenesis in plants and protein subcellular localization, DNA-damage response, and NF-κB activation in mammals. It is an evolutionarily conserved eight-protein complex with subunits CSN1 to CSN8 named following the descending order of molecular weights. Here, we report the crystal structure of the largest CSN subunit, CSN1 from Arabidopsis thaliana (atCSN1), which belongs to the Proteasome, COP9 signalosome, Initiation factor 3 (PCI) domain containing CSN subunit family, at 2.7 Å resolution. In contrast to previous predictions and distinct from the PCI-containing 26S proteasome regulatory particle subunit Rpn6 structure, the atCSN1 structure reveals an overall globular fold, with four domains consisting of helical repeat-I, linker helix, helical repeat-II, and the C-terminal PCI domain. Our small-angle X-ray scattering envelope of the CSN1-CSN7 complex agrees with the EM structure of the CSN alone (apo-CSN) and suggests that the PCI end of each molecule may mediate the interaction. Fitting of the CSN1 structure into the CSN-Skp1-Cul1-Fbox (SCF) EM structure shows that the PCI domain of CSN1 situates at the hub of the CSN for interaction with several other subunits whereas the linker helix and helical repeat-II of CSN1 contacts SCF using a conserved surface patch. Furthermore, we show that, in human, the C-terminal tail of CSN1, a segment not included in our crystal structure, interacts with IκBα in the NF-κB pathway. Therefore, the CSN complex uses multiple mechanisms to hinder NF-κB activation, a principle likely to hold true for its regulation of many other targets and pathways.T he constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is a more than 300-kDa complex that was first identified as a negative regulator of Constitutive Photomorphogenesis (COP) in plants (1, 2). In the subsequent years, the highly conserved protein complex was also found in fungi (3, 4), Caenorhabditis elegans (5), Drosophila melanogaster (6), and mammals (7,8). The most studied function of the CSN complex in eukaryotes is the regulation of protein degradation through two pathways, deneddylation (9-11) and deubiquitination (12, 13). In the deneddylation pathway, the CSN complex can influence the cullin-RING ligase activity by removing Nedd8, a ubiquitin-like protein, from a cullin (9, 14). On the other hand, the CSN complex can also suppress cullin activity through recruitment of the deubiquitination enzyme USP15 (12) or Ubp12p, the Schizosaccharomyces pombe ortholog of human USP15 (13). Other functions of the CSN complex identified in mammalian cells include regulating the phosphorylation of ubiquitin-proteasome pathway substrates through CSN-associated kinases (7,(15)(16)(17)(18). Overall, the CSN complex appears to be a key player in protein subcellular localization (19,20), DNA-damage response (21), NF-κB activation (22), development, and cell cycle control (23,24). Thus, the functions ...

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The Zinc Finger of the CSN-Associated Deubiquitinating Enzyme USP15 Is Essential to Rescue the E3 Ligase Rbx1

Cited by 133 publications

References 23 publications

The COP9 signalosome-mediated deneddylation is stimulated by caspases during apoptosis

The COP9 signalosome-mediated deneddylation is stimulated by caspases during apoptosis

Characterization of theVIER F-BOX PROTEINEGenes fromArabidopsisReveals Their Importance for Plant Growth and Development

Crystal structure and versatile functional roles of the COP9 signalosome subunit 1

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