CAND1 binds cytosolic CRL E3 ubiquitin ligases

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).<br>

CRL复合体由一个Cullin蛋白（人类中包括CUL1、2、3、4A、4B、5、7和9）和一个RING结构域蛋白（RBX1或2）组成，此外还包括一个或多个底物结合蛋白，这些蛋白赋予复合体底物特异性（详见Petoski和Deshaies，2005；Lipkowitz和Weismann，2011的研究）。根据其Cullin蛋白，CRL复合体可分为不同类别：CRL1复合体（亦称SCF复合体）包含CUL1，CRL2复合体包含CUL2，CLR复合体包含CUL3，而CLR5复合体包含CUL5。Cullin相关NEDD8解离蛋白1（CAND1，TIP120）是Cullin E3 RING泛素连接酶（CRL）复合体的关键组装因子，充当底物受体交换因子。CAND1通过Cullin亚基保守的氨基末端3个Cullin重复序列与无NEDD8修饰的CRL复合体结合，这些序列也是底物结合蛋白结合所必需的（Zheng等，2002a，b；Liu等2002；Min等，2003；Goldenberg等，2004）。通过破坏Cullin蛋白上的底物结合蛋白相互作用界面，CAND1的结合导致CRL复合体不稳定，从而允许底物结合蛋白的交换（Schmidt等，2009；Pierce等，2013；Zemla等，2013；Wu等，2013）。CRL复合体的Neddylation导致构象变化，消除了CAND1的结合位点，从而促进活性CRL泛素连接酶复合体的形成（Duda等，2008；Saha和Deshaies，2008；Boh等，2011；Yu等，2015）。