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Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process

Several bacterial and plant AB-toxins are delivered by retrograde vesicular transport to the endoplasmic reticulum (ER), where the enzymatically active A subunit is disassembled from the holotoxin and transported to the cytosol. In this process, toxins subvert the ER-associated degradation (ERAD) pa...

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Autores principales: Nowakowska-Gołacka, Jowita, Sominka, Hanna, Sowa-Rogozińska, Natalia, Słomińska-Wojewódzka, Monika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471375/
https://www.ncbi.nlm.nih.gov/pubmed/30875878
http://dx.doi.org/10.3390/ijms20061307
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author Nowakowska-Gołacka, Jowita
Sominka, Hanna
Sowa-Rogozińska, Natalia
Słomińska-Wojewódzka, Monika
author_facet Nowakowska-Gołacka, Jowita
Sominka, Hanna
Sowa-Rogozińska, Natalia
Słomińska-Wojewódzka, Monika
author_sort Nowakowska-Gołacka, Jowita
collection PubMed
description Several bacterial and plant AB-toxins are delivered by retrograde vesicular transport to the endoplasmic reticulum (ER), where the enzymatically active A subunit is disassembled from the holotoxin and transported to the cytosol. In this process, toxins subvert the ER-associated degradation (ERAD) pathway. ERAD is an important part of cellular regulatory mechanism that targets misfolded proteins to the ER channels, prior to their retrotranslocation to the cytosol, ubiquitination and subsequent degradation by a protein-degrading complex, the proteasome. In this article, we present an overview of current understanding of the ERAD-dependent transport of AB-toxins to the cytosol. We describe important components of ERAD and discuss their significance for toxin transport. Toxin recognition and disassembly in the ER, transport through ER translocons and finally cytosolic events that instead of overall proteasomal degradation provide proper folding and cytotoxic activity of AB-toxins are discussed as well. We also comment on recent reports presenting medical applications for toxin transport through the ER channels.
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spelling pubmed-64713752019-04-26 Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process Nowakowska-Gołacka, Jowita Sominka, Hanna Sowa-Rogozińska, Natalia Słomińska-Wojewódzka, Monika Int J Mol Sci Review Several bacterial and plant AB-toxins are delivered by retrograde vesicular transport to the endoplasmic reticulum (ER), where the enzymatically active A subunit is disassembled from the holotoxin and transported to the cytosol. In this process, toxins subvert the ER-associated degradation (ERAD) pathway. ERAD is an important part of cellular regulatory mechanism that targets misfolded proteins to the ER channels, prior to their retrotranslocation to the cytosol, ubiquitination and subsequent degradation by a protein-degrading complex, the proteasome. In this article, we present an overview of current understanding of the ERAD-dependent transport of AB-toxins to the cytosol. We describe important components of ERAD and discuss their significance for toxin transport. Toxin recognition and disassembly in the ER, transport through ER translocons and finally cytosolic events that instead of overall proteasomal degradation provide proper folding and cytotoxic activity of AB-toxins are discussed as well. We also comment on recent reports presenting medical applications for toxin transport through the ER channels. MDPI 2019-03-15 /pmc/articles/PMC6471375/ /pubmed/30875878 http://dx.doi.org/10.3390/ijms20061307 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Nowakowska-Gołacka, Jowita
Sominka, Hanna
Sowa-Rogozińska, Natalia
Słomińska-Wojewódzka, Monika
Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process
title Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process
title_full Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process
title_fullStr Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process
title_full_unstemmed Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process
title_short Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process
title_sort toxins utilize the endoplasmic reticulum-associated protein degradation pathway in their intoxication process
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471375/
https://www.ncbi.nlm.nih.gov/pubmed/30875878
http://dx.doi.org/10.3390/ijms20061307
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