Cargando…

Non-canonical activation of the ER stress sensor ATF6 by Legionella pneumophila effectors

The intracellular bacterial pathogen Legionella pneumophila (L.p.) secretes ∼330 effector proteins into the host cell to sculpt an ER-derived replicative niche. We previously reported five L.p. effectors that inhibit IRE1, a key sensor of the homeostatic unfolded protein response (UPR) pathway. In t...

Descripción completa

Detalles Bibliográficos
Autores principales: Ibe, Nnejiuwa U, Subramanian, Advait, Mukherjee, Shaeri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507491/
https://www.ncbi.nlm.nih.gov/pubmed/34635501
http://dx.doi.org/10.26508/lsa.202101247
_version_ 1784581868186763264
author Ibe, Nnejiuwa U
Subramanian, Advait
Mukherjee, Shaeri
author_facet Ibe, Nnejiuwa U
Subramanian, Advait
Mukherjee, Shaeri
author_sort Ibe, Nnejiuwa U
collection PubMed
description The intracellular bacterial pathogen Legionella pneumophila (L.p.) secretes ∼330 effector proteins into the host cell to sculpt an ER-derived replicative niche. We previously reported five L.p. effectors that inhibit IRE1, a key sensor of the homeostatic unfolded protein response (UPR) pathway. In this study, we discovered a subset of L.p. toxins that selectively activate the UPR sensor ATF6, resulting in its cleavage, nuclear translocation, and target gene transcription. In a deviation from the conventional model, this L.p.–dependent activation of ATF6 does not require its transport to the Golgi or its cleavage by the S1P/S2P proteases. We believe that our findings highlight the unique regulatory control that L.p. exerts upon the three UPR sensors and expand the repertoire of bacterial proteins that selectively perturb host homeostatic pathways.
format Online
Article
Text
id pubmed-8507491
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Life Science Alliance LLC
record_format MEDLINE/PubMed
spelling pubmed-85074912021-10-27 Non-canonical activation of the ER stress sensor ATF6 by Legionella pneumophila effectors Ibe, Nnejiuwa U Subramanian, Advait Mukherjee, Shaeri Life Sci Alliance Research Articles The intracellular bacterial pathogen Legionella pneumophila (L.p.) secretes ∼330 effector proteins into the host cell to sculpt an ER-derived replicative niche. We previously reported five L.p. effectors that inhibit IRE1, a key sensor of the homeostatic unfolded protein response (UPR) pathway. In this study, we discovered a subset of L.p. toxins that selectively activate the UPR sensor ATF6, resulting in its cleavage, nuclear translocation, and target gene transcription. In a deviation from the conventional model, this L.p.–dependent activation of ATF6 does not require its transport to the Golgi or its cleavage by the S1P/S2P proteases. We believe that our findings highlight the unique regulatory control that L.p. exerts upon the three UPR sensors and expand the repertoire of bacterial proteins that selectively perturb host homeostatic pathways. Life Science Alliance LLC 2021-10-11 /pmc/articles/PMC8507491/ /pubmed/34635501 http://dx.doi.org/10.26508/lsa.202101247 Text en © 2021 Ibe et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Ibe, Nnejiuwa U
Subramanian, Advait
Mukherjee, Shaeri
Non-canonical activation of the ER stress sensor ATF6 by Legionella pneumophila effectors
title Non-canonical activation of the ER stress sensor ATF6 by Legionella pneumophila effectors
title_full Non-canonical activation of the ER stress sensor ATF6 by Legionella pneumophila effectors
title_fullStr Non-canonical activation of the ER stress sensor ATF6 by Legionella pneumophila effectors
title_full_unstemmed Non-canonical activation of the ER stress sensor ATF6 by Legionella pneumophila effectors
title_short Non-canonical activation of the ER stress sensor ATF6 by Legionella pneumophila effectors
title_sort non-canonical activation of the er stress sensor atf6 by legionella pneumophila effectors
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507491/
https://www.ncbi.nlm.nih.gov/pubmed/34635501
http://dx.doi.org/10.26508/lsa.202101247
work_keys_str_mv AT ibennejiuwau noncanonicalactivationoftheerstresssensoratf6bylegionellapneumophilaeffectors
AT subramanianadvait noncanonicalactivationoftheerstresssensoratf6bylegionellapneumophilaeffectors
AT mukherjeeshaeri noncanonicalactivationoftheerstresssensoratf6bylegionellapneumophilaeffectors