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Gene Review

Cul1  -  cullin 1

Mus musculus

Synonyms: CUL-1, Cullin-1
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Disease relevance of Cul1

  • Relatively little is known about the function of the CUL-4A cullin, but its overexpression in breast cancer suggests CUL-4A might also regulate the cell cycle [1].

High impact information on Cul1

  • To study the role of Cul-1 in mammalian development and cell-cycle regulation, we generated mice deficient for Cul1 and analysed null embryos and heterozygous cell lines [2].
  • Using an in vitro assay for centriole separation in Xenopus extracts, antibodies to Skp1 or Cul1 block separation [3].
  • Using immunofluorescence microscopy, we show that in mammalian cells the Skp1 protein and the cullin Cul1 are localized to interphase and mitotic centrosomes and to the cytoplasm and nucleus [3].
  • Thus, the NEDD8 system is essential for the regulation of protein degradation pathways involved in cell cycle progression and morphogenesis, possibly through the function of the Cul family proteins [4].
  • Overall, the SOCS box and SH2 domain show a conserved spatial domain arrangement with the BC box and substrate recognition domain of the von Hippel-Lindau (VHL) tumor suppressor protein, suggesting a common mechanism of ubiquitination in these cullin-dependent E3 ligases [5].

Biological context of Cul1


Anatomical context of Cul1

  • Outgrowths of Cul1(-/-) blastocysts had limited proliferative capacity in vitro and accumulated cyclin E in all cells [6].
  • CD40 ligation compensated for CD22 deficiency by restoring lymphoblast development, proliferation, c-Myc and CUL1 expression, and protein ubiquitination/degradation in IgM-stimulated B6 CD22(-/-) B cell cultures [10].

Associations of Cul1 with chemical compounds

  • Mercury-containing sulfhydryl modification agents (rho-hydroxymercuribenzoate and mercuric chloride) irreversibly inhibit the ROC1-CUL1 ubiquitin ligase activity without disrupting the complex [11].

Other interactions of Cul1

  • SCF ubiquitin ligases, composed of three major subunits, Skp1, Cul1, and one of many F box proteins (Fbps), control the proteolysis of important cellular regulators [12].
  • That B6 CD22(-/-) B cells predominantly underwent apoptosis following IgM ligation correlated with this unique tolerant phenotype, as well as defective induction of the c-Myc:Cullin 1 (CUL1) ubiquitin ligase pathway that is necessary for progression to the S phase of cell cycle [10].


  1. Enforced expression of CUL-4A interferes with granulocytic differentiation and exit from the cell cycle. Li, B., Yang, F.C., Clapp, D.W., Chun, K.T. Blood (2003) [Pubmed]
  2. Loss of Cul1 results in early embryonic lethality and dysregulation of cyclin E. Dealy, M.J., Nguyen, K.V., Lo, J., Gstaiger, M., Krek, W., Elson, D., Arbeit, J., Kipreos, E.T., Johnson, R.S. Nat. Genet. (1999) [Pubmed]
  3. Components of an SCF ubiquitin ligase localize to the centrosome and regulate the centrosome duplication cycle. Freed, E., Lacey, K.R., Huie, P., Lyapina, S.A., Deshaies, R.J., Stearns, T., Jackson, P.K. Genes Dev. (1999) [Pubmed]
  4. The NEDD8 system is essential for cell cycle progression and morphogenetic pathway in mice. Tateishi, K., Omata, M., Tanaka, K., Chiba, T. J. Cell Biol. (2001) [Pubmed]
  5. Crystal structure of the SOCS2-elongin C-elongin B complex defines a prototypical SOCS box ubiquitin ligase. Bullock, A.N., Debreczeni, J.E., Edwards, A.M., Sundström, M., Knapp, S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Deletion of the Cul1 gene in mice causes arrest in early embryogenesis and accumulation of cyclin E. Wang, Y., Penfold, S., Tang, X., Hattori, N., Riley, P., Harper, J.W., Cross, J.C., Tyers, M. Curr. Biol. (1999) [Pubmed]
  7. Fbxw8 is essential for Cul1-Cul7 complex formation and for placental development. Tsunematsu, R., Nishiyama, M., Kotoshiba, S., Saiga, T., Kamura, T., Nakayama, K.I. Mol. Cell. Biol. (2006) [Pubmed]
  8. Involvement of an SCFSlmb complex in timely elimination of E2F upon initiation of DNA replication in Drosophila. Hériché, J.K., Ang, D., Bier, E., O'Farrell, P.H. BMC Genet. (2003) [Pubmed]
  9. Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A. Michel, J.J., Xiong, Y. Cell Growth Differ. (1998) [Pubmed]
  10. Severely impaired B lymphocyte proliferation, survival, and induction of the c-Myc:Cullin 1 ubiquitin ligase pathway resulting from CD22 deficiency on the C57BL/6 genetic background. Poe, J.C., Haas, K.M., Uchida, J., Lee, Y., Fujimoto, M., Tedder, T.F. J. Immunol. (2004) [Pubmed]
  11. The conserved RING-H2 finger of ROC1 is required for ubiquitin ligation. Chen, A., Wu, K., Fuchs, S.Y., Tan, P., Gomez, C., Pan, Z.Q. J. Biol. Chem. (2000) [Pubmed]
  12. Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo. Guardavaccaro, D., Kudo, Y., Boulaire, J., Barchi, M., Busino, L., Donzelli, M., Margottin-Goguet, F., Jackson, P.K., Yamasaki, L., Pagano, M. Dev. Cell (2003) [Pubmed]
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