He Yizhou Joseph, McCall Chad M, Hu Jian, Zeng Yaxue, Xiong Yue
Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, NC 27599, USA.
Genes Dev. 2006 Nov 1;20(21):2949-54. doi: 10.1101/gad.1483206.
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.
Cullin蛋白通过与ROC1及多种底物受体结合，组装成最大的泛素连接酶家族。CUL4的功能与许多细胞过程相关，但其底物招募机制仍不清楚。我们鉴定出一种蛋白质基序，即DWD框（与DDB1结合的WD40蛋白），并证明了15种DWD蛋白与DDB1-CUL4A的结合。我们提供的证据支持了DWD框的关键功能以及DDB1作为介导DWD蛋白与CUL4A结合的连接物的作用。数据库搜索预测，约三分之一的WD40蛋白（人类中有90种）含有DWD框，这表明可能存在大量的DWD-DDB1-CUL4-ROC1 E3连接酶。
