COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes

Stable Identifier
R-HSA-8956040
Type
Reaction
Species
Homo sapiens
Compartment
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Summation

The COP9 signalosome (also known as CSN) is a highly conserved multi-subunit enzymatic complex that plays a role as the sole CRL ubiquitin ligase deneddylase. Deneddylation decreases ubiquitin ligase activity of CRL complexes, and is required for the sCAND1 binding to the cullin subunit. The CSN is required for stabilization of CRL substrate receptors: without the CSN, CRL complexes are "hyper-active" and promote their own degradation through autoubiquitination. Both the CSN and CAND1 allow remodeling of the ubiquitin ligase complex through exchange of the ubiquitin substrate specific receptors (Cope et al, 2006; Denti et al, 2006; Peth et al, 2007; Schmidt et al, 2009; Enchev et al, 2012; Pierce et al, 2013; Zemla et al, 2013; Wu et al, 2013, reviewed in Wei et al, 2008). Deregulation of the CRL-CSN pathway causes misregulation of numerous important cellular targets and has been implicated in the development of some cancers (reviewed in Gummlich et al, 2013).

Literature References
PubMed ID Title Journal Year
17183367 COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase

Maine, GN, Mao, X, Komarck, CM, Burstein, E

EMBO J. 2007
23535662 CSN- and CAND1-dependent remodelling of the budding yeast SCF complex

Zemla, A, Thomas, Y, Kedziora, S, Knebel, A, Wood, NT, Rabut, G, Kurz, T

Nat Commun 2013
16401342 Targeted silencing of Jab1/Csn5 in human cells downregulates SCF activity through reduction of F-box protein levels

Cope, GA, Deshaies, RJ

BMC Biochem. 2006
18926707 The COP9 signalosome: more than a protease

Wei, N, Serino, G, Deng, XW

Trends Biochem. Sci. 2008
23535663 CAND1 controls in vivo dynamics of the cullin 1-RING ubiquitin ligase repertoire

Wu, S, Zhu, W, Nhan, T, Toth, JI, Petroski, MD, Wolf, DA

Nat Commun 2013
19748355 F-box-directed CRL complex assembly and regulation by the CSN and CAND1

Schmidt, MW, McQuary, PR, Wee, S, Hofmann, K, Wolf, DA

Mol. Cell 2009
18093314 Downregulation of COP9 signalosome subunits differentially affects the CSN complex and target protein stability

Peth, A, Berndt, C, Henke, W, Dubiel, W

BMC Biochem. 2007
23453757 Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins

Pierce, NW, Lee, JE, Liu, X, Sweredoski, MJ, Graham, RL, Larimore, EA, Rome, M, Zheng, N, Clurman, BE, Hess, S, Shan, SO, Deshaies, RJ

Cell 2013
23583660 Deregulation of the COP9 signalosome-cullin-RING ubiquitin-ligase pathway: mechanisms and roles in urological cancers

Gummlich, L, Rabien, A, Jung, K, Dubiel, W

Int. J. Biochem. Cell Biol. 2013
22959436 Structural basis for a reciprocal regulation between SCF and CSN

Enchev, RI, Scott, DC, da Fonseca, PC, Schreiber, A, Monda, JK, Schulman, BA, Peter, M, Morris, EP

Cell Rep 2012
16943200 The COP9 signalosome regulates Skp2 levels and proliferation of human cells

Denti, S, Fernández-Sánchez, ME, Rogge, L, Bianchi, E

J. Biol. Chem. 2006
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Catalyst Activity
Title
NEDD8-specific protease activity of COP9 [cytosol]
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Orthologous Events
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Reviewed