title: DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases.
abstract: 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.
authors.affiliation: Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Yizhou Joseph
authors.initials: YJ
authors.lastname: He
authors.forename: Chad M
authors.initials: CM
authors.lastname: McCall
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.forename: Yaxue
authors.initials: Y
authors.lastname: Zeng
authors.forename: Yue
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D017124:Conserved Sequence; D044842:Cullin Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: C114234:CUL4A protein, human; D002352:Carrier Proteins; D044842:Cullin Proteins; C091435:DDB1 protein, human; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; C479529:RBX1 protein, human; D044767:Ubiquitin-Protein Ligases