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DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases.

Cullins assemble the largest family of ubiquitin ligases by binding with ROC1 and various substrate receptors. CUL4 function is linked with many cellular processes, but its substrate-recruiting mechanism remains elusive. We identified a protein motif, the DWD box (DDB1-binding WD40 protein), and demonstrated the binding of 15 DWD proteins with DDB1-CUL4A. We provide evidence supporting the critical function of the DWD box and DDB1's role as the linker mediating DWD protein association with CUL4A. A database search predicts that about one-third of WD40 proteins, 90 in humans, contain the DWD box, suggesting a potentially large number of DWD-DDB1-CUL4-ROC1 E3 ligases.

Pubmed ID: 17079684


  • He YJ
  • McCall CM
  • Hu J
  • Zeng Y
  • Xiong Y


Genes & development

Publication Data

November 1, 2006

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM067113

Mesh Terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Carrier Proteins
  • Conserved Sequence
  • Cullin Proteins
  • DNA-Binding Proteins
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Ubiquitin-Protein Ligases