ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
HCV NS4B targets Scribble for proteasome-mediated degradation to facilitate cell transformation.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Viral subversion of the cell polarity regulator Scribble.Biochemical Society transactions · 2023Review
- Hepatitis C virus alters the morphology and function of peroxisomes.Frontiers in microbiology · 2023Article
- Impact of HCV Infection on Hepatocyte Polarity and Plasticity.Pathogens (Basel, Switzerland) · 2022Review
- Viral PDZ Binding Motifs Influence Cell Behavior Through the Interaction with Cellular Proteins Containing PDZ Domains.Methods in molecular biology (Clifton, N.J.) · 2021Review
- The bZIP Proteins of Oncogenic Viruses.Viruses · 2020Review
- Upsetting the Balance: When Viruses Manipulate Cell Polarity Control.Journal of molecular biology · 2018Review
- Hepatitis C virus NS4B protein induces epithelial-mesenchymal transition by upregulation of Snail.Virology journal · 2017Article
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Authors and funding
7 authors.
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Abstract
Hepatitis C virus (HCV) nonstructural protein 4B (NS4B) is a multi-transmembrane protein, but little is known about how NS4B contributes to HCV replication and tumorigenesis. Its C-terminal domain (CTD) has been shown to associate with intracellular membrane, and we have previously shown that NS4B CTD contains a class I PDZ-binding motif (PBM). Here, we demonstrated that NS4B PBM interacts with the PDZ-containing tumor suppressor protein, Scribble, using immunofluorescence and co-immunoprecipitation assays, and this interaction requires at least three contiguous PDZ domains of Scribble. In addition, NS4B PBM specifically induced Scribble degradation by activating the proteasome-ubiquitin pathway. Similar Scribble degradation was also observed in HCV-infected cells, suggesting NS4B could work in the context of HCV. Finally, NS4B PBM mutants showed reduced colony formation capacity compared with its wild-type counterpart, indicating that NS4B PBM plays important roles in NS4B-mediated cell transformation. 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.