title: Deubiquitylating enzymes and DNA damage response pathways.
abstract: Covalent post-translational modification of proteins by ubiquitin and ubiquitin-like factors has emerged as a general mechanism to regulate myriad intra-cellular processes. The addition and removal of ubiquitin or ubiquitin-like proteins from factors has recently been demonstrated as a key mechanism to modulate DNA damage response (DDR) pathways. It is thus, timely to evaluate the potential for ubiquitin pathway enzymes as DDR drug targets for therapeutic intervention. The synthetic lethal approach provides exciting opportunities for the development of targeted therapies to treat cancer: most tumours have lost critical DDR pathways, and thus rely more heavily on the remaining pathways, while normal tissues are still equipped with all DDR pathways. Here, we review key deubiquitylating enzymes (DUBs) involved in DDR pathways, and describe how targeting DUBs may lead to selective therapies to treat cancer patients.
authors.affiliation: MISSION Therapeutics Ltd, Babraham Research Campus, Cambridge, CB22 3AT, UK. xjacq@missiontherapeutics.com
authors.forename: Xavier
authors.initials: X
authors.lastname: Jacq
authors.forename: Mark
authors.initials: M
authors.lastname: Kemp
authors.forename: Niall M B
authors.initials: NM
authors.lastname: Martin
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Jackson
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases