id author title date pages extension mime words sentences flesch summary cache txt cord-006061-z9r5htm9 Hu, Bo HCV NS4B targets Scribble for proteasome-mediated degradation to facilitate cell transformation 2016-06-17 .txt text/plain 4242 242 53 Altogether, we provide a mechanism by which NS4B induces cell transformation through its PBM, which specifically interacts with the PDZ domains of Scribble and targets Scribble for degradation. Our previous work has shown that NS4B expression activates unfolded protein response (UPR), ER overload response, and NF-κB pathway in human hepatic cells, which could contribute to HCV replication and pathogenesis [11] [12] [13] . As shown in Fig. 5a , expression of HCV NS4B led to reduced USP14 protein levels in both 293T cells and HepG2 cells especially at 48-h post-transfection, indicating that HCV NS4B activates the proteasome-ubiquitin pathway. In this study, we provided a plausible mechanism that NS4B induces cell transformation by degrading the tumor-suppressor protein, Scribble, through the interaction between NS4B PBM and Scribble PDZ domains. The NS4B PBM-Scribble PDZ interaction is important for colony formation of transfected cells, indicating that NS4B PBM contributes to HCV pathogenesis and cellular transformation by inducing Scribble degradation. ./cache/cord-006061-z9r5htm9.txt ./txt/cord-006061-z9r5htm9.txt