Alternative titles; symbols
HGNC Approved Gene Symbol: CAND1
Cytogenetic location: 12q14.3-q15 Genomic coordinates (GRCh38) : 12:67,269,358-67,319,953 (from NCBI)
Using histidine-tagged TATA-binding protein (TBP; 600075) as a ligand for affinity-purification of TBP-interacting proteins, Yogosawa et al. (1996) purified a 120-kD protein, which they termed Tip120, from rat liver nuclear extracts. They obtained a full-length cDNA encoding Tip120 by screening a rat liver cDNA library. The rat Tip120 protein contains 1,230 amino acids and has a calculated molecular mass of 135 kD. Northern blot analysis detected a 4.5-kb transcript.
Yogosawa et al. (1996) showed that recombinant rat Tip120 interacted directly with TBP under a physiologic condition in vitro. Immunoprecipitation analysis indicated that Tip120 associated with TBP in nuclear extracts.
Zheng et al. (2002) isolated TIP120A as a cullin-1 (CUL1; 603134)-binding protein that they designated CAND1. They determined that the majority of CUL1 is in a complex with CAND1 and ROC1 (603814) independent of SKP1 (601434) and the F box protein SKP2 (601436). Both in vivo and in vitro, CAND1 prevented binding of SKP1 and SKP2 to CUL1, while dissociation of CAND1 from CUL1 promoted the reverse reaction. Neddylation of CUL1 or the presence of SKP1 and ATP caused CAND1 dissociation. These data suggested that CAND1 regulates the formation of the SCF (SKP1, CUL1/Cdc53, F box protein) complex and that its dissociation from CUL1 is coupled with the incorporation of F box proteins into the SCF complex, causing their destabilization.
Liu et al. (2002) showed that p120(CAND1) selectively binds to unneddylated CUL1 and is dissociated by CUL1 neddylation. CAND1 formed a ternary complex with CUL1 and ROC1. It dissociated SKP1 from CUL1 and inhibited SCF ligase activity in vitro. Suppression of CAND1 in vivo increased the level of the CUL1-SKP1 complex. The authors concluded that, by restricting SKP1-CUL1 interaction, CAND1 regulates the assembly of productive SCF ubiquitin ligases, allowing a common CUL1-ROC core to be utilized by a large number of SKP1-F box-substrate subcomplexes.
Min et al. (2005) stated that the COP9 signalosome (CSN; see 601934) inactivates SCF by catalyzing deconjugation of NEDD8 from CUL1. They found that CSN interacted with CUL1 irrespective of its neddylation state. Addition of CAND1, which bound only unneddylated CUL1, inhibited binding of CUL1 to CSN and enhanced the deneddylase activity of CSN in vitro.
By FISH, Yogosawa et al. (1999) mapped the CAND1 gene to chromosome 12q14.
Liu, J., Furukawa, M., Matsumoto, T., Xiong, Y. NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases. Molec. Cell 10: 1511-1518, 2002. [PubMed: 12504025] [Full Text: https://doi.org/10.1016/s1097-2765(02)00783-9]
Min, K.-W., Kwon, M.-J., Park, H.-S., Park, Y., Yoon, S. K., Yoon, J.-B. CAND1 enhances deneddylation of CUL1 by COP9 signalosome. Biochem. Biophys. Res. Commun. 334: 867-874, 2005. [PubMed: 16036220] [Full Text: https://doi.org/10.1016/j.bbrc.2005.06.188]
Yogosawa, S., Kayukawa, K., Kawata, T., Makino, Y., Inoue, S., Okuda, A., Muramatsu, M., Tamura, T. Induced expression, localization, and chromosome mapping of a gene for the TBP-interacting protein 120A. Biochem. Biophys. Res. Commun. 266: 123-128, 1999. [PubMed: 10581176] [Full Text: https://doi.org/10.1006/bbrc.1999.1773]
Yogosawa, S., Makino, Y., Yoshida, T., Kishimoto, T., Muramatsu, M., Tamura, T. Molecular cloning of a novel 120-kDa TBP-interacting protein. Biochem. Biophys. Res. Commun. 229: 612-617, 1996. [PubMed: 8954946] [Full Text: https://doi.org/10.1006/bbrc.1996.1852]
Zheng, J., Yang, X., Harrell, J. M., Ryzhikov, S., Shim, E.-H., Lykke-Andersen, K., Wei, N., Sun, H., Kobayashi, R., Zhang, H. CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex. Molec. Cell 10: 1519-1526, 2002. [PubMed: 12504026] [Full Text: https://doi.org/10.1016/s1097-2765(02)00784-0]