USP Antibody Sampler Kit

Background

Ubiquitinating enzymes (UBEs) catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action (1,2). The ubiquitin-specific protease (USP) subfamily is one of five distinct groups of DUB enzymes. Ubiquitin-specific-processing protease 1 (USP1) is regulated in a cell cycle dependent manner by both transcriptional and ubiquitin-proteasomal mechanisms (3). Nuclear USP1 localizes to chromatin where it deubiquitinates monoubiquitinated FANCD2 and plays an important role in DNA damage repair and Chk1 protein stability (3,4). Ubiquitin-specific-processing protease 2 (USP2) contains C19 peptidase activity and is involved in ubiquitin recycling and disassembly of polymeric ubiquitin and ubiquitin-like protein complexes (5). USP2 is a putative oncoprotein that is highly over expressed in prostate cancer and drives tumor growth by binding and stabilizing fatty acid synthase through deubiquitination (6,7).

Herpesvirus-associated ubiquitin-specific protease (HAUSP, USP7) binds and deubiquitinates transcription factor p53 and regulator protein Mdm2, stabilizing both proteins (8,9). HAUSP modifies other ubiquitinated proteins, including FoxO family forkhead transcription factors and the mitotic stress checkpoint protein CHFR (10,11). Ubiquitin-specific protease 8 (USP8, UBPy) is a cysteine protease and growth-regulated enzyme that is essential for cell proliferation and survival (12,13). The catalytic domain of USP9X possesses cysteine peptidase activity that cleaves ubiquitin and polyubiquitin conjugates. USP9X may help stabilize adherens and tight junction molecules during epithelial cell polarization (14,15). USP10 is regulated at the posttranslational level through protein-protein interactions and phosphorylation. Interaction of USP10 with the Ras-GAP SH3 domain binding protein (G3BP) inhibits the ability of USP10 to catalyze ubiquitin chain disassembly (16). ATM-mediated phosphorylation of USP10 at Thr42 and Ser337 promotes USP10 stabilization and relocation from the cytoplasm to the nucleus, where it functions in p53 deubiquitination, stabilization, and activation in response to genotoxic stress (17).

USP14 is recruited to the proteasome through association with the PSMD2 (S2/hRPN1) subunit of the 19S regulatory particle, where it may antagonize substrate degradation (18,19). USP14 trims ubiquitin residues from distal polyubiquitin chain ends, decreasing chain affinity for proteasome ubiquitin receptors and allowing for enhanced substrate stability (20,21). USP18 (UBP43) catalyzes the removal of the interferon-regulated, ubiquitin-like protein ISG15 from conjugated proteins (22). Removal of ISG15 from target proteins maintains a critical balance of cellular ISG15-conjugated proteins, which is important for normal development and brain function (23,24). USP28 can bind, deubiquitinate and stabilize several DNA-damage pathway proteins, including p53BP1 and Chk2 (25). USP28 plays an important role in Myc-related signaling as it catalyzes Myc deubiquitination and promotes Myc stabilization, which contributes to tumor-cell growth (26).