Reactome | COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes

COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes

Stable Identifier

R-HSA-8956040

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

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COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes

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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