文献类型：期刊文献

英文题名：Disease Association and Druggability of WD40 Repeat Proteins

作者：Song, Richard[1];Wang, Zhong-Duo[1,3];Schapira, Matthieu[1,2]

机构：[1]Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada;[2]Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON M5S 1A8, Canada;[3]Guangdong Ocean Univ, Fisheries Coll, Zhanjiang 524025, Guangdong, Peoples R China

年份：2017

卷号：16

期号：10

起止页码：3766

外文期刊名：JOURNAL OF PROTEOME RESEARCH

收录：SCI-EXPANDED(收录号：WOS:000412789400026)、、WOS

基金：The SGC is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada through Ontario Genomics Institute [OGI-055], Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766], Janssen, Merck & Co., Novartis Pharma AG, Ontario Ministry of Research, Innovation and Science (MRIS), Pfizer, sao Paulo Research Foundation-FAPESP, Takeda, and the Wellcome Trust.

语种：英文

外文关键词：WD40; WDR; cancer; disease association; druggability; regulation of transcription; ubiquitin proteasome system; therapeutic target; human proteome; CRISPR knockout screen

外文摘要：WD40 repeat (WDR) domains are protein interaction scaffolds that represent one of the largest protein families in human, and a first WDR inhibitor-an allosteric antagonist of polycomb repressive complex 2-just entered the clinic. A systematic analysis of the CORUM database of protein complexes shows that WDR is the most represented domain in transcriptional regulation and one of the most prevalent in the ubiquitin proteasome system, two pathways of high relevance to drug discovery. Parsing the literature and the vulnerability of cancer cell lines to CRISPR knockout indicates that WDR proteins are targets of interest in oncology and other disease areas. A quantitative analysis of WDR structures reveals that druggable binding pockets can be found on multiple surfaces of these multifaceted protein interaction platforms. These data support the development of chemical probes to further interrogate WDR proteins as an emerging therapeutic target class.