Integrating multi-omics data reveals function and therapeutic potential of deubiquitinating enzymes

• DOI: 10.7554/elife.72879
• Publication Date: 2022-06-23T11:00:33Z
• Authors: Laura M Doherty; Caitlin E Mills; Sarah A Boswell; Xiaoxi Liu; Charles Tapley Hoyt; Benjamin Gyori; Sara J Buhrlage; Peter K Sorger
• Keywords: Deubiquitinating enzyme

Deubiquitinating enzymes (DUBs), ~100 of which are found in human cells, proteases that remove ubiquitin conjugates from proteins, thereby regulating protein turnover. They involved a wide range cellular activities and emerging therapeutic targets for cancer other diseases. Drugs targeting USP1 USP30 clinical development kidney disease respectively. However, the majority substrates pathways regulated by DUBs remain unknown, impeding efforts to prioritize specific research drug development. To assemble knowledgebase DUB activities, co-dependent genes, substrates, we combined targeted experiments using CRISPR libraries inhibitors with systematic mining functional genomic databases. Analysis Dependency Map, Connectivity Cancer Cell Line Encyclopedia, multiple protein-protein interaction databases yielded hypotheses about function, subset were confirmed follow-on experiments. The data this paper browsable online newly developed Portal promise improve understanding as family well incompletely characterized (e.g. USPL1 USP32) those already investigational therapeutics USP14, UCHL5, USP7).