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Degradation of AIMP1/p43 Induced by Hepatitis C Virus E2 Leads to Upregulation of TGF-β Signaling and Increase in Surface Expression of gp96

Hepatitis C virus (HCV) causes chronic hepatitis leading to liver fibrosis and autoimmune diseases. AIMP1/p43 is a multifunctional protein initially known as a cofactor of aminoacyl tRNA synthetase complex. Its function includes negative regulation of TGF-β signaling and suppression of Lupus-like au...

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Autores principales: Kim, Min Soo, Kim, Sunghoon, Myung, Heejoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015952/
https://www.ncbi.nlm.nih.gov/pubmed/24816397
http://dx.doi.org/10.1371/journal.pone.0096302
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author Kim, Min Soo
Kim, Sunghoon
Myung, Heejoon
author_facet Kim, Min Soo
Kim, Sunghoon
Myung, Heejoon
author_sort Kim, Min Soo
collection PubMed
description Hepatitis C virus (HCV) causes chronic hepatitis leading to liver fibrosis and autoimmune diseases. AIMP1/p43 is a multifunctional protein initially known as a cofactor of aminoacyl tRNA synthetase complex. Its function includes negative regulation of TGF-β signaling and suppression of Lupus-like autoimmune disease by inhibition of surface expression of gp96. HCV E2 was shown to directly interact with AIMP1/p43 by GST pulldown assay and coimmunoprecipitation. Their subcellular colocalization was observed in an immunofluorescence confocal microscopy. We showed that HCV E2 led to degradation of AIMP1/p43 in two ways. First, in the presence of HCV E2, endogenous AIMP1/p43 was shown to be degraded in an ubiquitin-dependent proteasome pathway. Second, grp78, an ER chaperone, was shown to interact with and stabilize AIMP1/p43. And HCV E2 inhibited this interaction leading to reduction of cellular AIMP1/p43. The degradation of AIMP1/p43 by HCV E2 resulted in increase of TGF-β signaling and cell surface expression of gp96. Thus we suggest that these are novel mechanisms responsible for liver fibrosis and autoimmune diseases caused by HCV.
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spelling pubmed-40159522014-05-14 Degradation of AIMP1/p43 Induced by Hepatitis C Virus E2 Leads to Upregulation of TGF-β Signaling and Increase in Surface Expression of gp96 Kim, Min Soo Kim, Sunghoon Myung, Heejoon PLoS One Research Article Hepatitis C virus (HCV) causes chronic hepatitis leading to liver fibrosis and autoimmune diseases. AIMP1/p43 is a multifunctional protein initially known as a cofactor of aminoacyl tRNA synthetase complex. Its function includes negative regulation of TGF-β signaling and suppression of Lupus-like autoimmune disease by inhibition of surface expression of gp96. HCV E2 was shown to directly interact with AIMP1/p43 by GST pulldown assay and coimmunoprecipitation. Their subcellular colocalization was observed in an immunofluorescence confocal microscopy. We showed that HCV E2 led to degradation of AIMP1/p43 in two ways. First, in the presence of HCV E2, endogenous AIMP1/p43 was shown to be degraded in an ubiquitin-dependent proteasome pathway. Second, grp78, an ER chaperone, was shown to interact with and stabilize AIMP1/p43. And HCV E2 inhibited this interaction leading to reduction of cellular AIMP1/p43. The degradation of AIMP1/p43 by HCV E2 resulted in increase of TGF-β signaling and cell surface expression of gp96. Thus we suggest that these are novel mechanisms responsible for liver fibrosis and autoimmune diseases caused by HCV. Public Library of Science 2014-05-09 /pmc/articles/PMC4015952/ /pubmed/24816397 http://dx.doi.org/10.1371/journal.pone.0096302 Text en © 2014 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kim, Min Soo
Kim, Sunghoon
Myung, Heejoon
Degradation of AIMP1/p43 Induced by Hepatitis C Virus E2 Leads to Upregulation of TGF-β Signaling and Increase in Surface Expression of gp96
title Degradation of AIMP1/p43 Induced by Hepatitis C Virus E2 Leads to Upregulation of TGF-β Signaling and Increase in Surface Expression of gp96
title_full Degradation of AIMP1/p43 Induced by Hepatitis C Virus E2 Leads to Upregulation of TGF-β Signaling and Increase in Surface Expression of gp96
title_fullStr Degradation of AIMP1/p43 Induced by Hepatitis C Virus E2 Leads to Upregulation of TGF-β Signaling and Increase in Surface Expression of gp96
title_full_unstemmed Degradation of AIMP1/p43 Induced by Hepatitis C Virus E2 Leads to Upregulation of TGF-β Signaling and Increase in Surface Expression of gp96
title_short Degradation of AIMP1/p43 Induced by Hepatitis C Virus E2 Leads to Upregulation of TGF-β Signaling and Increase in Surface Expression of gp96
title_sort degradation of aimp1/p43 induced by hepatitis c virus e2 leads to upregulation of tgf-β signaling and increase in surface expression of gp96
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015952/
https://www.ncbi.nlm.nih.gov/pubmed/24816397
http://dx.doi.org/10.1371/journal.pone.0096302
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