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Gene Review

CUL4A  -  cullin 4A

Homo sapiens

Synonyms: CUL-4A, Cullin-4A
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Disease relevance of CUL4A


High impact information on CUL4A


Biological context of CUL4A

  • In human cells, inactivation of CUL4A induces CDK inhibitor p27(Kip1) stabilization and G(1) cell cycle arrest which is dependent on the presence of p27, suggesting that this regulatory pathway is evolutionarily conserved [9].
  • These findings identify DDB subunits as the first substrates of the CUL-4A ubiquitination machinery and suggest that abnormal expression of Cul-4A results in reduced p48 levels, thus impairing the ability of DDB in lesion recognition and DNA repair in tumor cells [10].
  • Despite 87% similarity between the Cul-4A and Cul-4B cullins, the CUL-4A(-/-) lethal phenotype indicates that CUL-4A has one or more distinct function(s) [4].

Anatomical context of CUL4A

  • However, CUL-4A(-/-) blastocysts are viable, hatch, form an inner cell mass and trophectoderm, and implant (roughly 4.5 dpc), indicating that CUL-4A(-/-) embryos die between 4.5 and 7.5 dpc [4].

Other interactions of CUL4A

  • In conclusion, our findings suggest that TFDP1, CUL4A, and CDC16 are probable targets of an amplification mechanism and therefore may be involved, together or separately, in development and/or progression of some HCCs [1].
  • Cullin 4A associates with the UV-damaged DNA-binding protein DDB [2].
  • CUL-4A is a member of the cullin family of proteins, which are believed to be ubiquitin-protein isopeptide ligases (type E3) [2].
  • Recently we found that NEDD8, a ubiquitin-like protein, was linked covalently to human cullin-4A (abbreviated Cul-4A) by a new ubiquitin-related pathway that is analogous to but distinct from the ligating system for SUMO1, another ubiquitin-like protein [11].
  • Unlike HOXA9, the NUP98-HOXA9 fusion was protected from ubiquitination mediated by Cullin-4A and subsequent proteasome-dependent degradation [12].


  1. TFDP1, CUL4A, and CDC16 identified as targets for amplification at 13q34 in hepatocellular carcinomas. Yasui, K., Arii, S., Zhao, C., Imoto, I., Ueda, M., Nagai, H., Emi, M., Inazawa, J. Hepatology (2002) [Pubmed]
  2. Cullin 4A associates with the UV-damaged DNA-binding protein DDB. Shiyanov, P., Nag, A., Raychaudhuri, P. J. Biol. Chem. (1999) [Pubmed]
  3. The xeroderma pigmentosum group E gene product DDB2 is a specific target of cullin 4A in mammalian cells. Nag, A., Bondar, T., Shiv, S., Raychaudhuri, P. Mol. Cell. Biol. (2001) [Pubmed]
  4. CUL-4A is critical for early embryonic development. Li, B., Ruiz, J.C., Chun, K.T. Mol. Cell. Biol. (2002) [Pubmed]
  5. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Groisman, R., Polanowska, J., Kuraoka, I., Sawada, J., Saijo, M., Drapkin, R., Kisselev, A.F., Tanaka, K., Nakatani, Y. Cell (2003) [Pubmed]
  6. A new NEDD8-ligating system for cullin-4A. Osaka, F., Kawasaki, H., Aida, N., Saeki, M., Chiba, T., Kawashima, S., Tanaka, K., Kato, S. Genes Dev. (1998) [Pubmed]
  7. CUL-4A stimulates ubiquitylation and degradation of the HOXA9 homeodomain protein. Zhang, Y., Morrone, G., Zhang, J., Chen, X., Lu, X., Ma, L., Moore, M., Zhou, P. EMBO J. (2003) [Pubmed]
  8. The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites. Kapetanaki, M.G., Guerrero-Santoro, J., Bisi, D.C., Hsieh, C.L., Rapić-Otrin, V., Levine, A.S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  9. Involvement of CUL4 ubiquitin E3 ligases in regulating CDK inhibitors Dacapo/p27Kip1 and cyclin E degradation. Higa, L.A., Yang, X., Zheng, J., Banks, D., Wu, M., Ghosh, P., Sun, H., Zhang, H. Cell Cycle (2006) [Pubmed]
  10. UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation. Chen, X., Zhang, Y., Douglas, L., Zhou, P. J. Biol. Chem. (2001) [Pubmed]
  11. Covalent modification of all members of human cullin family proteins by NEDD8. Hori, T., Osaka, F., Chiba, T., Miyamoto, C., Okabayashi, K., Shimbara, N., Kato, S., Tanaka, K. Oncogene (1999) [Pubmed]
  12. Enforced expression of NUP98-HOXA9 in human CD34(+) cells enhances stem cell proliferation. Chung, K.Y., Morrone, G., Schuringa, J.J., Plasilova, M., Shieh, J.H., Zhang, Y., Zhou, P., Moore, M.A. Cancer Res. (2006) [Pubmed]
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