Figure 2. Various roles of DUBs in oncology.
Selected, representative examples of deubiquitylating enzymes (DUBs; light blue ovals) involved in distinct cellular pathways and regulation of various ubiquitylated substrates (dark blue ovals) related to oncology. The proteasome and associated DUBs facilitate protein turnover and recycle ubiquitin. Ubiquitin-specific protease 28 (USP28) regulates turnover of the oncogene product MYC, ataxin 3 (ATXN3) controls the stability of the tumour suppressor p53, and USP7 regulates p53 and its E3 ubiquitin ligase human double minute 2 (HDM2). USP1, USP4 and USP11 have important roles in DNA damage repair, whereas USP9X regulates claspin and is linked to replication stress and checkpoint signalling. BRCA1-associated protein 1 (BAP1) and USP22 participate in chromatin remodelling by deubiquitylating histones, and ubiquitin carboxy-terminal hydrolase-like 1 (UCHL1) plays a part in AKT signalling. These are representative examples only and not meant to be exhaustive. Examples of small-molecule compounds targeting these DUBs are shown. BRCA1, breast cancer type 1 susceptibility protein; CTIP, C-terminal-binding protein-interacting protein; FANCD2, Fanconi anaemia group D2 protein; GFR, growth factor receptor; MRE11, meiotic recombination 11 homologue 1; NBS1, Nijmegen breakage syndrome protein 1; PALB2, partner and localizer of BRCA2; PCNA, proliferating cell nuclear antigen; PI3K, phosphoinositide 3-kinase.