Reactome | CAND1 binds cytosolic CRL E3 ubiquitin ligases

CAND1 binds cytosolic CRL E3 ubiquitin ligases

Stable Identifier

R-HSA-8955241

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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CAND1 binds cytosolic CRL E3 ubiquitin ligases

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CRL complexes consist of a cullin protein (CUL1, 2, 3, 4A, 4B, 5, 7 and 9 in humans) and a RING box protein (RBX1 or 2) in addition to one or more substrate binding proteins that confer substrate specificity to the complex (reviewed in Petroski and Deshaies, 2005; Lipkowitz and Weismann, 2011). CRL complexes can be classes according to their cullin proteins: CRL1 complexes (also called SCF complexes) contain CUL1, CRL2 complexes contain CUL2, CLR complexes contain CUL3, and CLR5 complexes contain CUL5. Cullin-associated NEDD8-dissociated protein 1 (CAND1, TIP120) is a key assembly factor of Cullin E3 RING ubiquitin ligase (CRL) complexes, acting as a substrate receptor exchange factor. CAND1 binds to the inactive, deneddylated CRL complex through the conserved amino-terminal 3 Cullin repeats of the cullin subunit, which are also required for binding of the substrate binding proteins (Zheng et al, 2002a, b; Liu et al 2002; Min et al, 2003; Goldenberg et al, 2004). By disrupting the substrate binding protein interaction interface on the cullin proteins, CAND1 binding destabilizes the CRL complex, allowing exchange of the substrate binding protein (Schmidt et al, 2009; Pierce et al, 2013; Zemla et al, 2013; Wu et al, 2013). Neddylation of the CRL complex results in a conformational change that eliminates the CAND1 binding site, thereby promoting the active CRL ubiquitin ligase complex (Duda et al, 2008; Saha and Deshaies, 2008; Boh et al, 2011; Yu et al, 2015).

Literature References

PubMed ID	Title	Journal	Year
21463634	Neddylation-induced conformational control regulates cullin RING ligase activity in vivo Boh, BK, Hagen, T, Smith, PG	J. Mol. Biol.	2011
18851830	Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation Saha, A, Deshaies, RJ	Mol. Cell	2008
15688063	Function and regulation of cullin-RING ubiquitin ligases Petroski, MD, Deshaies, RJ	Nat. Rev. Mol. Cell Biol.	2005
12504025	NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases Furukawa, M, Liu, J, Xiong, Y, Matsumoto, T	Mol. Cell	2002
21863050	RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis Lipkowitz, S, Weissman, AM	Nat. Rev. Cancer	2011
23535662	CSN- and CAND1-dependent remodelling of the budding yeast SCF complex Wood, NT, Knebel, A, Rabut, G, Kedziora, S, Thomas, Y, Kurz, T, Zemla, A	Nat Commun	2013
12609982	TIP120A associates with cullins and modulates ubiquitin ligase activity Park, Y, Min, KW, Hwang, JW, Lee, JS, Tamura, TA, Yoon, JB	J. Biol. Chem.	2003
11961546	Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex Chu, C, Pagano, M, Song, L, Wang, P, Pavletich, NP, Miller, JJ, Elledge, SJ, Jeffrey, PD, Schulman, BA, Conaway, JW, Koepp, DM, Zheng, N, Conaway, RC, Harper, JW	Nature	2002
23535663	CAND1 controls in vivo dynamics of the cullin 1-RING ubiquitin ligase repertoire Wu, S, Petroski, MD, Nhan, T, Wolf, DA, Toth, JI, Zhu, W	Nat Commun	2013
19748355	F-box-directed CRL complex assembly and regulation by the CSN and CAND1 Hofmann, K, Wee, S, Schmidt, MW, McQuary, PR, Wolf, DA	Mol. Cell	2009
23453757	Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins Hess, S, Zheng, N, Graham, RL, Clurman, BE, Sweredoski, MJ, Shan, SO, Rome, M, Pierce, NW, Larimore, EA, Deshaies, RJ, Liu, X, Lee, JE	Cell	2013
15537541	Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases Liu, J, Cascio, TC, Zheng, N, Xiong, Y, Shumway, SD, Garbutt, KC, Goldenberg, SJ	Cell	2004
26632597	Gln40 deamidation blocks structural reconfiguration and activation of SCF ubiquitin ligase complex by Nedd8 Zheng, N, Mao, H, Rychnovsky, SD, Novitsky, EJ, Huang, L, Yu, C, Tang, X	Nat Commun	2015
18805092	Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation Borg, LA, Hunt, HW, Duda, DM, Schulman, BA, Hammel, M, Scott, DC	Cell	2008
12504026	CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex Lykke-Andersen, K, Harrell, JM, Ryzhikov, S, Sun, H, Wei, N, Shim, EH, Zheng, J, Zhang, H, Yang, X, Kobayashi, R	Mol. Cell	2002