COP9 signalosome deneddylates nuclear CRL4 E3 ubiquitin ligase complex

Stable Identifier
R-HSA-8956045
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
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 subsequent binding of CAND1 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
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
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
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
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
Participants
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
NEDD8-specific protease activity of COP9 signalosome [nucleoplasm]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed