损伤特异性DNA结合蛋白1（DDB1）作为一种连接物，将受体WD40蛋白招募至CUL4-ROC1泛素连接酶。
DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases.
作者信息
He Yizhou Joseph, McCall Chad M, Hu Jian, Zeng Yaxue, Xiong Yue
机构信息
Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, NC 27599, USA.
出版信息
Genes Dev. 2006 Nov 1;20(21):2949-54. doi: 10.1101/gad.1483206.
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.
摘要
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。
相似文献
1
DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases.损伤特异性DNA结合蛋白1（DDB1）作为一种连接物，将受体WD40蛋白招募至CUL4-ROC1泛素连接酶。
Genes Dev. 2006 Nov 1;20(21):2949-54. doi: 10.1101/gad.1483206.
2
Characterization of Arabidopsis and rice DWD proteins and their roles as substrate receptors for CUL4-RING E3 ubiquitin ligases.拟南芥和水稻DWD蛋白的特性及其作为CUL4-RING E3泛素连接酶底物受体的作用。
Plant Cell. 2008 Jan;20(1):152-67. doi: 10.1105/tpc.107.055418. Epub 2008 Jan 25.
3
Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery.DDB1-CUL4A泛素连接酶机制的分子结构与组装
Nature. 2006 Oct 5;443(7111):590-3. doi: 10.1038/nature05175.
4
WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase.WD40蛋白FBW5通过DDB1-CUL4-ROC1连接酶促进肿瘤抑制因子TSC2的泛素化。
Genes Dev. 2008 Apr 1;22(7):866-71. doi: 10.1101/gad.1624008.
5
Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development.1型人类免疫缺陷病毒Vpr结合蛋白VprBP是一种与DDB1-CUL4 E3泛素连接酶相关的WD40蛋白，对DNA复制和胚胎发育至关重要。
Mol Cell Biol. 2008 Sep;28(18):5621-33. doi: 10.1128/MCB.00232-08. Epub 2008 Jul 7.
6
CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation.CUL4-DDB1泛素连接酶与多种WD40重复蛋白相互作用并调节组蛋白甲基化。
Nat Cell Biol. 2006 Nov;8(11):1277-83. doi: 10.1038/ncb1490. Epub 2006 Oct 15.
7
Arabidopsis DDB1-CUL4 ASSOCIATED FACTOR1 forms a nuclear E3 ubiquitin ligase with DDB1 and CUL4 that is involved in multiple plant developmental processes.拟南芥DDB1 - CUL4相关因子1与DDB1和CUL4形成一种核E3泛素连接酶，参与多种植物发育过程。
Plant Cell. 2008 Jun;20(6):1437-55. doi: 10.1105/tpc.108.058891. Epub 2008 Jun 13.
8
L2DTL/CDT2 and PCNA interact with p53 and regulate p53 polyubiquitination and protein stability through MDM2 and CUL4A/DDB1 complexes.L2DTL/CDT2和增殖细胞核抗原（PCNA）与p53相互作用，并通过MDM2和CUL4A/DDB1复合物调节p53的多聚泛素化和蛋白质稳定性。
Cell Cycle. 2006 Aug;5(15):1719-29. doi: 10.4161/cc.5.15.3150. Epub 2006 Aug 1.
9
A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1.一类多样的与Cul4-Ddb1相互作用的蛋白质包括Cdt2，它是复制因子Cdt1在S期被破坏所必需的。
Mol Cell. 2006 Sep 1;23(5):709-21. doi: 10.1016/j.molcel.2006.08.010.
10
CRL4s: the CUL4-RING E3 ubiquitin ligases.CRL4s：CUL4-RING E3 泛素连接酶。
Trends Biochem Sci. 2009 Nov;34(11):562-70. doi: 10.1016/j.tibs.2009.07.002. Epub 2009 Oct 7.
引用本文的文献
1
OICR-41103 as a chemical probe for the DCAF1 WD40 domain.OICR-41103作为DCAF1 WD40结构域的化学探针。
Commun Biol. 2025 Jul 19;8(1):1076. doi: 10.1038/s42003-025-08491-0.
2
Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes.恶性疟原虫两种Cullin-RING连接酶复合物中各组分的功能表征
Sci Rep. 2025 Jul 1;15(1):21359. doi: 10.1038/s41598-025-05342-0.
3
Molecular glue degrader for tumor treatment.用于肿瘤治疗的分子胶降解剂。
Front Oncol. 2024 Dec 12;14:1512666. doi: 10.3389/fonc.2024.1512666. eCollection 2024.
4
Principles of paralog-specific targeted protein degradation engaging the C-degron E3 KLHDC2.利用 C 降解基序 E3 KLHDC2 进行旁系同源特异性靶向蛋白降解的原理。
Nat Commun. 2024 Oct 12;15(1):8829. doi: 10.1038/s41467-024-52966-3.
5
Acetylation- and ubiquitination-regulated SFMBT2 acts as a tumor suppressor in clear cell renal cell carcinoma.乙酰化和泛素化调节的 SFMBT2 作为一种肿瘤抑制因子在透明细胞肾细胞癌中发挥作用。
Biol Direct. 2024 May 11;19(1):37. doi: 10.1186/s13062-024-00480-3.
6
Development of Peptide Displacement Assays to Screen for Antagonists of DDB1 Interactions.开发肽置换测定法筛选 DDB1 相互作用的拮抗剂。
Biochemistry. 2024 May 21;63(10):1297-1306. doi: 10.1021/acs.biochem.4c00044. Epub 2024 May 10.
7
Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF.靶向 DCAF5 通过稳定 SWI/SNF 抑制 SMARCB1 突变型癌症。
Nature. 2024 Apr;628(8007):442-449. doi: 10.1038/s41586-024-07250-1. Epub 2024 Mar 27.
8
Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.泛素及类泛素修饰在癌症治疗中的功能、机制与药物发现及多组学分析
Acta Pharm Sin B. 2023 Nov;13(11):4341-4372. doi: 10.1016/j.apsb.2023.07.019. Epub 2023 Jul 22.
9
An inventory of crosstalk between ubiquitination and other post-translational modifications in orchestrating cellular processes.泛素化与其他翻译后修饰在协调细胞过程中的相互作用清单。
iScience. 2023 Feb 26;26(5):106276. doi: 10.1016/j.isci.2023.106276. eCollection 2023 May 19.
10
Discovery of Nanomolar DCAF1 Small Molecule Ligands.发现纳摩尔 DCAF1 小分子配体。
J Med Chem. 2023 Apr 13;66(7):5041-5060. doi: 10.1021/acs.jmedchem.2c02132. Epub 2023 Mar 22.
本文引用的文献
1
Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery.DDB1-CUL4A泛素连接酶机制的分子结构与组装
Nature. 2006 Oct 5;443(7111):590-3. doi: 10.1038/nature05175.
2
A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1.一类多样的与Cul4-Ddb1相互作用的蛋白质包括Cdt2，它是复制因子Cdt1在S期被破坏所必需的。
Mol Cell. 2006 Sep 1;23(5):709-21. doi: 10.1016/j.molcel.2006.08.010.
3
Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase.与副粘病毒V蛋白复合的DDB1结构：泛素连接酶中螺旋桨簇的病毒劫持
Cell. 2006 Jan 13;124(1):105-17. doi: 10.1016/j.cell.2005.10.033.
4
Transactivation of Schizosaccharomyces pombe cdt2+ stimulates a Pcu4-Ddb1-CSN ubiquitin ligase.粟酒裂殖酵母cdt2+的反式激活刺激Pcu4-Ddb1-CSN泛素连接酶。
EMBO J. 2005 Nov 16;24(22):3940-51. doi: 10.1038/sj.emboj.7600854. Epub 2005 Oct 27.
5
Ddb1 controls genome stability and meiosis in fission yeast.Ddb1控制裂殖酵母中的基因组稳定性和减数分裂。
Genes Dev. 2005 Apr 1;19(7):853-62. doi: 10.1101/gad.329905.
6
Function and regulation of cullin-RING ubiquitin ligases.泛素连接酶Cullin-RING的功能与调控
Nat Rev Mol Cell Biol. 2005 Jan;6(1):9-20. doi: 10.1038/nrm1547.
7
VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases.VHL结构域和SOCS结构域决定了对泛素连接酶的Cul2-Rbx1和Cul5-Rbx2模块的结合特异性。
Genes Dev. 2004 Dec 15;18(24):3055-65. doi: 10.1101/gad.1252404.
8
Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases.Cand1-Cul1-Roc1复合物的结构揭示了多亚基cullin依赖性泛素连接酶组装的调控机制。
Cell. 2004 Nov 12;119(4):517-28. doi: 10.1016/j.cell.2004.10.019.
9
Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage.响应DNA损伤时，DDB1-CUL4A-ROC1连接酶对CDT1进行靶向泛素化修饰。
Nat Cell Biol. 2004 Oct;6(10):1003-9. doi: 10.1038/ncb1172. Epub 2004 Sep 26.
10
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase.人类去黄化蛋白1通过组装CUL4A泛素连接酶来调控c-Jun。
Science. 2004 Feb 27;303(5662):1371-4. doi: 10.1126/science.1093549. Epub 2004 Jan 22.
Zotero 插件