ArticleThe Journal of biological chemistry2013
Hepatitis C virus NS5A inhibits mixed lineage kinase 3 to block apoptosis.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Amino acid substitutions in norovirus VP1 dictate host dissemination via variations in cellular attachment.Journal of virology · 2023Article
- ASPP2 binds to hepatitis C virus NS5A protein via an SH3 domain/PxxP motif-mediated interaction and potentiates infection.The Journal of general virology · 2023Article
- Article
- The regulatory function of mixed lineage kinase 3 in tumor and host immunity.Pharmacology & therapeutics · 2021Review
- Voltage-Gated Potassium Channels as Regulators of Cell Death.Frontiers in cell and developmental biology · 2020Review
- Baicalin relieves inflammation stimulated by lipopolysaccharide via upregulating TUG1 in liver cells.Journal of physiology and biochemistry · 2019Article
- Kinases: Understanding Their Role in HIV Infection.World journal of AIDS · 2019Article
- MC159 of Molluscum Contagiosum Virus Suppresses Autophagy by Recruiting Cellular SH3BP4 via an SH3 Domain-Mediated Interaction.Journal of virology · 2019Article
- Identification of two distinct peptide-binding pockets in the SH3 domain of human mixed-lineage kinase 3.The Journal of biological chemistry · 2018Article
- Mixed-lineage kinase 3 pharmacological inhibition attenuates murine nonalcoholic steatohepatitis.JCI insight · 2017Article
- Oxidation of KCNB1 potassium channels triggers apoptotic integrin signaling in the brain.Cell death & disease · 2017Article
- Large-Scale Screening of Preferred Interactions of Human Src Homology-3 (SH3) Domains Using Native Target Proteins as Affinity Ligands.Molecular & cellular proteomics : MCP · 2016Article
- Mixed lineage kinase 3 mediates release of C-X-C motif ligand 10-bearing chemotactic extracellular vesicles from lipotoxic hepatocytes.Hepatology (Baltimore, Md.) · 2016Article
- Ankyrin Repeat Domain 1 is Up-regulated During Hepatitis C Virus Infection and Regulates Hepatitis C Virus Entry.Scientific reports · 2016Article
- Ion Channels and Oxidative Stress as a Potential Link for the Diagnosis or Treatment of Liver Diseases.Oxidative medicine and cellular longevity · 2016Review
- Hepatitis C virus NS5A protein blocks epidermal growth factor receptor degradation via a proline motif- dependent interaction.The Journal of general virology · 2015Article
- Vinexin β Interacts with Hepatitis C Virus NS5A, Modulating Its Hyperphosphorylation To Regulate Viral Propagation.Journal of virology · 2015Article
- Requirement for chloride channel function during the hepatitis C virus life cycle.Journal of virology · 2015Article
- Oxidative stress and hepatic Nox proteins in chronic hepatitis C and hepatocellular carcinoma.Free radical biology & medicine · 2014Review
- Mechanisms of hepatocarcinogenesis in chronic hepatitis C.Hepatic oncology · 2014Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatitis C virus (HCV) infection results in the activation of numerous stress responses including oxidative stress, with the potential to induce an apoptotic state. Previously we have shown that HCV attenuates the stress-induced, p38MAPK-mediated up-regulation of the K(+) channel Kv2.1, to maintain the survival of infected cells in the face of cellular stress. We demonstrated that this effect was mediated by HCV non-structural 5A (NS5A) protein, which impaired p38MAPK activity through a polyproline motif-dependent interaction, resulting in reduction of phosphorylation activation of Kv2.1. In this study, we investigated the host cell proteins targeted by NS5A to mediate Kv2.1 inhibition. We screened a phage-display library expressing the entire complement of human SH3 domains for novel NS5A-host cell interactions. This analysis identified mixed lineage kinase 3 (MLK3) as a putative NS5A interacting partner. MLK3 is a serine/threonine protein kinase that is a member of the MAPK kinase kinase (MAP3K) family and activates p38MAPK. An NS5A-MLK3 interaction was confirmed by co-immunoprecipitation and Western blot analysis. We further demonstrate a novel role of MLK3 in the modulation of Kv2.1 activity, whereby MLK3 overexpression leads to the up-regulation of channel activity. Accordingly, coexpression of NS5A suppressed this stimulation. Additionally we demonstrate that overexpression of MLK3 induced apoptosis, which was also counteracted by NS5A. We conclude that NS5A targets MLK3 with multiple downstream consequences for both apoptosis and K(+) homeostasis.
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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.