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Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes

Shiga-toxigenic Escherichia coli (STEC) use subtilase cytotoxin (SubAB) to interfere with adaptive immunity. Its inhibition of immunoglobulin secretion is both rapid and profound. SubAB favors cleavage of the newly synthesized immunoglobulin heavy chain–binding protein (BiP) to yield a C-terminal fr...

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Autores principales: Hu, Chih-Chi Andrew, Dougan, Stephanie K., Winter, Sebastian Virreira, Paton, Adrienne W., Paton, James C., Ploegh, Hidde L.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768844/
https://www.ncbi.nlm.nih.gov/pubmed/19808260
http://dx.doi.org/10.1084/jem.20090782
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author Hu, Chih-Chi Andrew
Dougan, Stephanie K.
Winter, Sebastian Virreira
Paton, Adrienne W.
Paton, James C.
Ploegh, Hidde L.
author_facet Hu, Chih-Chi Andrew
Dougan, Stephanie K.
Winter, Sebastian Virreira
Paton, Adrienne W.
Paton, James C.
Ploegh, Hidde L.
author_sort Hu, Chih-Chi Andrew
collection PubMed
description Shiga-toxigenic Escherichia coli (STEC) use subtilase cytotoxin (SubAB) to interfere with adaptive immunity. Its inhibition of immunoglobulin secretion is both rapid and profound. SubAB favors cleavage of the newly synthesized immunoglobulin heavy chain–binding protein (BiP) to yield a C-terminal fragment that contains BiP’s substrate-binding domain. In the absence of its regulatory nucleotide-binding domain, the SubAB-cleaved C-terminal BiP fragment remains tightly bound to newly synthesized immunoglobulin light chains, resulting in retention of light chains in the endoplasmic reticulum (ER). Immunoglobulins are thus detained in the ER, making impossible the secretion of antibodies by SubAB-treated B cells. The inhibitory effect of SubAB is highly specific for antibody secretion, because other secretory proteins such as IL-6 are released normally from SubAB-treated B cells. Although SubAB also causes BiP cleavage in HepG2 hepatoma cells, (glyco)protein secretion continues unabated in SubAB-exposed HepG2 cells. This specific block in antibody secretion is a novel means of immune evasion for STEC. The differential cleavage of newly synthesized versus “aged” BiP by SubAB in the ER provides insight into the architecture of the ER compartments involved.
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spelling pubmed-27688442010-04-26 Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes Hu, Chih-Chi Andrew Dougan, Stephanie K. Winter, Sebastian Virreira Paton, Adrienne W. Paton, James C. Ploegh, Hidde L. J Exp Med Article Shiga-toxigenic Escherichia coli (STEC) use subtilase cytotoxin (SubAB) to interfere with adaptive immunity. Its inhibition of immunoglobulin secretion is both rapid and profound. SubAB favors cleavage of the newly synthesized immunoglobulin heavy chain–binding protein (BiP) to yield a C-terminal fragment that contains BiP’s substrate-binding domain. In the absence of its regulatory nucleotide-binding domain, the SubAB-cleaved C-terminal BiP fragment remains tightly bound to newly synthesized immunoglobulin light chains, resulting in retention of light chains in the endoplasmic reticulum (ER). Immunoglobulins are thus detained in the ER, making impossible the secretion of antibodies by SubAB-treated B cells. The inhibitory effect of SubAB is highly specific for antibody secretion, because other secretory proteins such as IL-6 are released normally from SubAB-treated B cells. Although SubAB also causes BiP cleavage in HepG2 hepatoma cells, (glyco)protein secretion continues unabated in SubAB-exposed HepG2 cells. This specific block in antibody secretion is a novel means of immune evasion for STEC. The differential cleavage of newly synthesized versus “aged” BiP by SubAB in the ER provides insight into the architecture of the ER compartments involved. The Rockefeller University Press 2009-10-26 /pmc/articles/PMC2768844/ /pubmed/19808260 http://dx.doi.org/10.1084/jem.20090782 Text en © 2009 Hu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Hu, Chih-Chi Andrew
Dougan, Stephanie K.
Winter, Sebastian Virreira
Paton, Adrienne W.
Paton, James C.
Ploegh, Hidde L.
Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes
title Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes
title_full Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes
title_fullStr Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes
title_full_unstemmed Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes
title_short Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes
title_sort subtilase cytotoxin cleaves newly synthesized bip and blocks antibody secretion in b lymphocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768844/
https://www.ncbi.nlm.nih.gov/pubmed/19808260
http://dx.doi.org/10.1084/jem.20090782
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