InterPro domain: IPR039852

This entry includes cullin-associated NEDD8-dissociated proteins 1 (CAND1 also known as TIP120A) and 2 (CAND2); these proteins have a C-terminal TATA-binding protein interacting (TIP20) domain. CAND1 is required for the assembly of the SCF E3 ubiquitin ligase complex. The SCF ubiquitin E3 ligase consists of SKP1, CUL1 and F-box protein, and it regulates ubiquitin-dependent proteolysis. CAND1 binds to CUL1, preventing it from associating with the other components that form the ligase. Neddylation of CUL1 (or the presence of SKP1 and ATP) dissociates it from CAND1, allowing the ligase complex to form [ 1 , 2 , 3 ]. CAND1 also interacts with CUL3, a component of the Cul3-dependent E3 ubiquitin ligase complex [ 4 ]. CAND1 has been proposed to be an F-box protein exchange factor, and as substrates of the ligase complex are degraded by the proteasome and depleted, the ligase complex enters an intermediate, deneddylated state when CAND1 can bind, promoting dissociation of the substrate-recognition subunit and recruitment of a new substrate-recognition subunit [ 5 ]. CAND2 is uncharacterized but is assumed to have similar roles to CAND1.

1. CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex. Mol. Cell 10, 1519-26
2. NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases. Mol. Cell 10, 1511-8
3. TIP120A associates with cullins and modulates ubiquitin ligase activity. J. Biol. Chem. 278, 15905-10
4. CAND1-mediated substrate adaptor recycling is required for efficient repression of Nrf2 by Keap1. Mol. Cell. Biol. 26, 1235-44
5. Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins. Cell 153, 206-15