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Gene Review

CAND1  -  cullin-associated and neddylation...

Homo sapiens

Synonyms: Cullin-associated NEDD8-dissociated protein 1, Cullin-associated and neddylation-dissociated protein 1, DKFZp434M1414, KIAA0829, TBP-interacting protein 120A, ...
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Disease relevance of CAND1


High impact information on CAND1

  • At one end, a Cand1 beta hairpin protrusion partially occupies the adaptor binding site on Cul1, inhibiting its interactions with the Skp1 adaptor and the substrate-recruiting F box protein subunits [5].
  • Cand1, a 120 kDa HEAT repeat protein, forms a tight complex with the Cul1-Roc1 SCF catalytic core, inhibiting the assembly of the multisubunit E3 complex [5].
  • Deletion analysis demonstrated that a 412-residue N-terminal domain, which includes an acidic region and the TBP-binding domain, is required for TIP120 function [6].
  • Interestingly, TIP120 also stimulates RNAP I- and III-driven transcription and binds to RPB5, one of the common subunits of the eukaryotic RNA polymerases, in vitro [6].
  • Our x-ray crystallographic studies of the C-terminal domain of FANCF reveal a helical repeat structure similar to the Cand1 regulator of the Cul1-Rbx1-Skp1-Fbox(Skp2) ubiquitin ligase complex [7].

Biological context of CAND1


Anatomical context of CAND1

  • In a search for proteins involved in regulation of cullin-containing E3 ubiquitin ligases we immunopurified CUL4B-containing complex from HeLa cells and identified TIP120A as an associated protein by mass spectrometry [10].
  • TIP120A transcripts were expressed abundantly in the heart and liver, moderately in the brain and skeletal muscle, and only slightly in the spleen and lung [1].
  • Biochemical and co-transfection studies revealed that TIP120B, but not the closely related protein TIP120A, is a specific substrate of KIAA10 in vitro and within C2C12 myoblasts but not in Cos-1 cells [11].
  • We found that TIP120B gene was induced in C2C12 myoblasts when these cells differentiated into myotubes, whereas TIP120A gene expression was down-regulated [12].
  • The highest extent of information relevant to the discrimination between patients and normal subjects is obtained following stimulation of lymphocytes with Cand and in decreasing order with PPD, SK-SD and PHA [13].

Associations of CAND1 with chemical compounds

  • Arabidopsis ETA2, an apparent ortholog of the human cullin-interacting protein CAND1, is required for auxin responses mediated by the SCF(TIR1) ubiquitin ligase [14].
  • The level of TIP120A was also elevated in such stem-like cells as F9 and HL60 after each differentiation procedure, retinoic acid and DMSO, respectively [1].
  • Using histidine-tagged TBP as a ligand for affinity-purification of proteins bound to TBP, we purified a 120-kD protein, termed TBP-interacting protein 120 (TIP120), from rat liver nuclear extracts [8].
  • TIP120A binds to TBP in the acidic amino acid-rich N-terminal region and in the leucine-rich C-terminal region [15].
  • These effects of L-NMMA were not affected significantly by pretreatment with CAND [16].

Physical interactions of CAND1

  • Previous biochemical studies of CAND1 have suggested that it specifically binds to unmodified CUL1 to negatively regulate SCF assembly [14].

Enzymatic interactions of CAND1


Other interactions of CAND1

  • Suppression of CAND1 in vivo increased the level of the CUL1-SKP1 complex [17].
  • Furthermore, TIP120A was shown to interact selectively with Cul1 that is not modified by NEDD8 [18].

Analytical, diagnostic and therapeutic context of CAND1

  • Immunoprecipitation of cullins revealed that all cullins tested specifically interacted with TIP120A [10].
  • Electrophoretic mobility shift assays showed that TIP120 enhanced PIC formation, and TIP120 also stimulated the nonspecific transcription and DNA-binding activity of RNAP II [6].
  • If the 1:8 titer for the colonized patient with a contaminated arterial line is not considered a false-positive result, the CAND-TEC sensitivity was 83% [19].
  • GST pull-down and yeast two-hybrid assays demonstrated that hNOT3L is associated with TIP120B but not with TIP120A [12].
  • To determine the timing to initiate antifungal chemotherapy, we performed the CAND-TEC assay serially in each patient [20].


  1. Induced expression, localization, and chromosome mapping of a gene for the TBP-interacting protein 120A. Yogosawa, S., Kayukawa, K., Kawata, T., Makino, Y., Inoue, S., Okuda, A., Muramatsu, M., Tamura, T. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  2. High prevalence of HPV 16 in South African women with cancer of the cervix and cervical intraepithelial neoplasia. Kay, P., Soeters, R., Nevin, J., Denny, L., Dehaeck, C.M., Williamson, A.L. J. Med. Virol. (2003) [Pubmed]
  3. Trichosporon cutaneum fungemia in patients with acute myeloblastic leukemia and measurement of serum D-arabinitol, Candida antigen (CAND-TEC), and beta-D-glucan. Morimoto, S., Shimazaki, C., Goto, H., Hirata, Y., Tasumi, T., Yamagata, N., Hirata, T., Ashihara, E., Inaba, T., Fujita, N. Ann. Hematol. (1994) [Pubmed]
  4. HIV Coinfection with Hepatitis Cand Hepatitis B. Smith, J.O., Sterling, R.K. Current infectious disease reports. (2006) [Pubmed]
  5. Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases. Goldenberg, S.J., Cascio, T.C., Shumway, S.D., Garbutt, K.C., Liu, J., Xiong, Y., Zheng, N. Cell (2004) [Pubmed]
  6. TATA-Binding protein-interacting protein 120, TIP120, stimulates three classes of eukaryotic transcription via a unique mechanism. Makino, Y., Yogosawa, S., Kayukawa, K., Coin, F., Egly, J.M., Wang, Z., Roeder, R.G., Yamamoto, K., Muramatsu, M., Tamura, T. Mol. Cell. Biol. (1999) [Pubmed]
  7. Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complex. Kowal, P., Gurtan, A.M., Stuckert, P., D'Andrea, A.D., Ellenberger, T. J. Biol. Chem. (2007) [Pubmed]
  8. Molecular cloning of a novel 120-kDa TBP-interacting protein. Yogosawa, S., Makino, Y., Yoshida, T., Kishimoto, T., Muramatsu, M., Tamura, T. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  9. Expression of antiapoptotic and proapoptotic molecules in diabetic retinas. Abu El-Asrar, A.M., Dralands, L., Missotten, L., Geboes, K. Eye (London, England) (2007) [Pubmed]
  10. TIP120A associates with cullins and modulates ubiquitin ligase activity. Min, K.W., Hwang, J.W., Lee, J.S., Park, Y., Tamura, T.A., Yoon, J.B. J. Biol. Chem. (2003) [Pubmed]
  11. Proteolytic targeting of transcriptional regulator TIP120B by a HECT domain E3 ligase. You, J., Wang, M., Aoki, T., Tamura, T.A., Pickart, C.M. J. Biol. Chem. (2003) [Pubmed]
  12. TBP-interacting protein 120B, which is induced in relation to myogenesis, binds to NOT3. Aoki, T., Okada, N., Wakamatsu, T., Tamura, T.A. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  13. Lymphocyte reactivity in healthy subjects and cancer patients. Haasz, R., Robinson, E. Acta Haematol. (1977) [Pubmed]
  14. Arabidopsis ETA2, an apparent ortholog of the human cullin-interacting protein CAND1, is required for auxin responses mediated by the SCF(TIR1) ubiquitin ligase. Chuang, H.W., Zhang, W., Gray, W.M. Plant Cell (2004) [Pubmed]
  15. TBP-interacting protein TIP120A is a new global transcription activator with bipartite functional domains. Kayukawa, K., Kitajima, Y., Tamura, T. Genes Cells (2001) [Pubmed]
  16. The systemic and renal response to NO inhibition is not modified by angiotensin-II-receptor blockade in healthy humans. Bech, J.N., Svendsen, K.B., Nielsen, C.B., Pedersen, E.B. Nephrol. Dial. Transplant. (1999) [Pubmed]
  17. NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases. Liu, J., Furukawa, M., Matsumoto, T., Xiong, Y. Mol. Cell (2002) [Pubmed]
  18. Preferential interaction of TIP120A with Cul1 that is not modified by NEDD8 and not associated with Skp1. Oshikawa, K., Matsumoto, M., Yada, M., Kamura, T., Hatakeyama, S., Nakayama, K.I. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  19. Candida detection system (CAND-TEC) to differentiate between Candida albicans colonization and disease. Fung, J.C., Donta, S.T., Tilton, R.C. J. Clin. Microbiol. (1986) [Pubmed]
  20. Surveillance of the serum Candida antigen titer for initiation of antifungal therapy after post-remission chemotherapy in patients with acute leukemia. Iwasaki, H., Misaki, H., Nakamura, T., Ueda, T. Int. J. Hematol. (2000) [Pubmed]
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