CAND1 binds cytosolic CRL E3 ubiquitin ligases

Stable Identifier
Reaction [binding]
Homo sapiens
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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
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