ArticleMolecular biology of the cell2013
SHIP2 regulates epithelial cell polarity through its lipid product, which binds to Dlg1, a pathway subverted by hepatitis C virus core protein.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Viral subversion of the cell polarity regulator Scribble.Biochemical Society transactions · 2023Review
- Deletion of p38γ attenuates ethanol consumption- and acetaminophen-induced liver injury in mice through promoting Dlg1.Acta pharmacologica Sinica · 2022Article
- Impact of HCV Infection on Hepatocyte Polarity and Plasticity.Pathogens (Basel, Switzerland) · 2022Review
- Review
- Membrane Lipids in Epithelial Polarity: Sorting out the PIPs.Frontiers in cell and developmental biology · 2022Review
- Targeting PDZ domains as potential treatment for viral infections, neurodegeneration and cancer.Biology direct · 2021Review
- Host PDZ-containing proteins targeted by SARS-CoV-2.The FEBS journal · 2021Article
- Role of PDZ-binding motif from West Nile virus NS5 protein on viral replication.Scientific reports · 2021Article
- SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility.The Journal of cell biology · 2019Article
- Article
- The interaction between CASK and the tumour suppressor Dlg1 regulates mitotic spindle orientation in mammalian epithelia.Journal of cell science · 2019Article
- PDZ Domains as Drug Targets.Advanced therapeutics · 2019Review
- Mesenchymal-epithelial transition in development and reprogramming.Nature cell biology · 2019Review
- The phospholipid PI(3,4)PNature communications · 2018Article
- Upsetting the Balance: When Viruses Manipulate Cell Polarity Control.Journal of molecular biology · 2018Review
- INPPL1 gene mutations in opsismodysplasia.Journal of human genetics · 2017Review
- PI3K/SHIP2/PTEN pathway in cell polarity and hepatitis C virus pathogenesis.World journal of hepatology · 2017Review
- Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV.Nature communications · 2016Article
- Viral Interactions with PDZ Domain-Containing Proteins-An Oncogenic Trait?Pathogens (Basel, Switzerland) · 2016Review
- Structural and functional hepatocyte polarity and liver disease.Journal of hepatology · 2015Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The main targets of hepatitis C virus (HCV) are hepatocytes, the highly polarized cells of the liver, and all the steps of its life cycle are tightly dependent on host lipid metabolism. The interplay between polarity and lipid metabolism in HCV infection has been poorly investigated. Signaling lipids, such as phosphoinositides (PIs), play a vital role in polarity, which depends on the distribution and expression of PI kinases and PI phosphatases. In this study, we report that HCV core protein, expressed in Huh7 and Madin-Darby canine kidney (MDCK) cells, disrupts apicobasal polarity. This is associated with decreased expression of the polarity protein Dlg1 and the PI phosphatase SHIP2, which converts phosphatidylinositol 3,4,5-trisphosphate into phosphatidylinositol 4,5-bisphosphate (PtdIns(3,4)P2). SHIP2 is mainly localized at the basolateral membrane of polarized MDCK cells. In addition, PtdIns(3,4)P2 is able to bind to Dlg1. SHIP2 small interfering RNA or its catalytically dead mutant disrupts apicobasal polarity, similar to HCV core. In core-expressing cells, RhoA activity is inhibited, whereas Rac1 is activated. Of interest, SHIP2 expression rescues polarity, RhoA activation, and restricted core level in MDCK cells. We conclude that SHIP2 is an important regulator of polarity, which is subverted by HCV in epithelial cells. It is suggested that SHIP2 could be a promising target for anti-HCV treatment.
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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.