2005
DOI: 10.1111/j.1742-4658.2005.04807.x
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Consequences of COP9 signalosome and 26S proteasome interaction

Abstract: The COP9 signalosome (CSN) occurs in all eukaryotic cells. It is a regulatory particle of the ubiquitin (Ub)/26S proteasome system. The eight subunits of the CSN possess sequence homologies with the polypeptides of the 26S proteasome lid complex and just like the lid, the CSN consists of six subunits with PCI (proteasome, COP9 signalosome, initiation factor 3) domains and two components with MPN (Mpr‐Pad1‐N‐terminal) domains. Here we show that the CSN directly interacts with the 26S proteasome and competes wit… Show more

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Cited by 66 publications
(77 citation statements)
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“…Integration of CSN5 into the CSN complex and the consequent protein-protein interactions with CSN subunits such as CSN6, as highlighted by nondenaturing MS experiments (5), are likely to play a part in both CSN5 activation and substrate recruitment. Given the body of evidence (30)(31)(32)(33) that supports the involvement of multiple CSN subunits in substrate recruitment (e.g., the interaction between CSN2 and cullin 1), the observed difference in activity between the CSN complex and the stand-alone R106T CSN5 could be directly linked to the presence of substrate recruitment exosites remote from CSN5 catalytic site, achieving optimal activation and contributing to productive binding of Nedd8-cullin isopeptide bond. Supported by our work, CSN5 incorporation into the CSN complex probably does not lead to global structural reshaping of the enzyme.…”
Section: Discussionmentioning
confidence: 99%
“…Integration of CSN5 into the CSN complex and the consequent protein-protein interactions with CSN subunits such as CSN6, as highlighted by nondenaturing MS experiments (5), are likely to play a part in both CSN5 activation and substrate recruitment. Given the body of evidence (30)(31)(32)(33) that supports the involvement of multiple CSN subunits in substrate recruitment (e.g., the interaction between CSN2 and cullin 1), the observed difference in activity between the CSN complex and the stand-alone R106T CSN5 could be directly linked to the presence of substrate recruitment exosites remote from CSN5 catalytic site, achieving optimal activation and contributing to productive binding of Nedd8-cullin isopeptide bond. Supported by our work, CSN5 incorporation into the CSN complex probably does not lead to global structural reshaping of the enzyme.…”
Section: Discussionmentioning
confidence: 99%
“…In brief, 2 x 10 7 cells were lyzed in mono-lysis buffer [33] and equal amounts (3 mg) were loaded onto a 12 ml glycerol gradient (10 -40%). Fractions of 600 µl were collected and aliquots used for Western blot analysis with the indicated antibodies.…”
Section: Glycerol Gradients and Non-denaturing Electrophoresismentioning
confidence: 99%
“…The CSN assembles with CRLs into super-complexes [33,36,37], in which CSN6 interacts with Rbx1 and CSN2 with cullins [5,6]. We were interested to see whether besides CSN6 additional components of the CSN-CRL complexes were modified by activated caspases during apoptosis.…”
Section: Caspase Cleavage Of Csn6 Is Accompanied By Cleavage Of Rbx1mentioning
confidence: 99%
“…of Anatomy and Cell Biology, Aulweg 123, 35385 Giessen,; E-mail: andreas.meinhardt@ anatomie.med.uni-giessen.de. 5 The abbreviations used are: Ub, ubiquitin; AAA ϩ , ATPase associated with various cellular activities; APS, ammonium persulfate. BisTris, 2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol; CLSM, confocal laser scanning microscopy; CSN, COP9 signalosome; FRET, fluorescence resonance energy transfer; GST, glutathione S-transferase; IP, immunoprecipitation; MPN domain, MOV34/PAD N-terminal domain; JAMM, Jab1/MPN domain-associated metallopeptidase; mCSN5, deneddylasedefective mutant; MIF, macrophage migration inhibitory factor; Ni-NTA, nickel-nitrilotriacetic acid; p97/VCP, p97/valosin-containing protein; ROI, region of interest; RP, regulatory particle; siRNA, small interfering RNA; TEMED, N,N,NЈ,NЈ-tetramethylethylenediamine; UBX, ubiquitin regulatory X; UPS, ubiquitin/proteasome system.…”
mentioning
confidence: 99%
“…Many fundamental cellular functions such as membrane fusion, gene transcription, DNA replication, and repair are controlled by the covalent linkage of ubiquitin (Ub) 5 to substrate proteins (1). Different Ub modifications serve as signaling-dependent regulators of protein interaction networks (2).…”
mentioning
confidence: 99%