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Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones
The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Pseudomonas aeruginosa. Here, we report the use of photoactive probes to identify MVP as a target of the N-(3-oxo-dodecanoyl) homoserin...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000436/ https://www.ncbi.nlm.nih.gov/pubmed/33723037 http://dx.doi.org/10.1073/pnas.2012529118 |
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author | Rayo, Josep Gregor, Rachel Jacob, Nicholas T. Dandela, Rambabu Dubinsky, Luba Yashkin, Alex Aranovich, Alexander Thangaraj, Manikandan Ernst, Orna Barash, Eran Malitsky, Sergey Florea, Bogdan I. Krom, Bastiaan P. Wiemer, Erik A. C. Kickhoefer, Valerie A. Rome, Leonard H. Mathison, John C. Kaufmann, Gunnar F. Overkleeft, Herman S. Cravatt, Benjamin F. Zor, Tsaffrir Janda, Kim D. Ulevitch, Richard J. Kravchenko, Vladimir V. Meijler, Michael M. |
author_facet | Rayo, Josep Gregor, Rachel Jacob, Nicholas T. Dandela, Rambabu Dubinsky, Luba Yashkin, Alex Aranovich, Alexander Thangaraj, Manikandan Ernst, Orna Barash, Eran Malitsky, Sergey Florea, Bogdan I. Krom, Bastiaan P. Wiemer, Erik A. C. Kickhoefer, Valerie A. Rome, Leonard H. Mathison, John C. Kaufmann, Gunnar F. Overkleeft, Herman S. Cravatt, Benjamin F. Zor, Tsaffrir Janda, Kim D. Ulevitch, Richard J. Kravchenko, Vladimir V. Meijler, Michael M. |
author_sort | Rayo, Josep |
collection | PubMed |
description | The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Pseudomonas aeruginosa. Here, we report the use of photoactive probes to identify MVP as a target of the N-(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing signal of certain proteobacteria including P. aeruginosa. A treatment of normal and cancer cells with C12 or other N-acyl homoserine lactones (AHLs) results in rapid translocation of MVP into lipid raft (LR) membrane fractions. Like AHLs, inflammatory stimuli also induce LR-localization of MVP, but the C12 stimulation reprograms (functionalizes) bioactivity of the plasma membrane by recruiting death receptors, their apoptotic adaptors, and caspase-8 into LR. These functionalized membranes control AHL-induced signaling processes, in that MVP adjusts the protein kinase p38 pathway to attenuate programmed cell death. Since MVP is the structural core of large particles termed vaults, our findings suggest a mechanism in which MVP vaults act as sentinels that fine-tune inflammation-activated processes such as apoptotic signaling mediated by immunosurveillance cytokines including tumor necrosis factor-related apoptosis inducing ligand (TRAIL). |
format | Online Article Text |
id | pubmed-8000436 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-80004362021-04-01 Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones Rayo, Josep Gregor, Rachel Jacob, Nicholas T. Dandela, Rambabu Dubinsky, Luba Yashkin, Alex Aranovich, Alexander Thangaraj, Manikandan Ernst, Orna Barash, Eran Malitsky, Sergey Florea, Bogdan I. Krom, Bastiaan P. Wiemer, Erik A. C. Kickhoefer, Valerie A. Rome, Leonard H. Mathison, John C. Kaufmann, Gunnar F. Overkleeft, Herman S. Cravatt, Benjamin F. Zor, Tsaffrir Janda, Kim D. Ulevitch, Richard J. Kravchenko, Vladimir V. Meijler, Michael M. Proc Natl Acad Sci U S A Biological Sciences The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Pseudomonas aeruginosa. Here, we report the use of photoactive probes to identify MVP as a target of the N-(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing signal of certain proteobacteria including P. aeruginosa. A treatment of normal and cancer cells with C12 or other N-acyl homoserine lactones (AHLs) results in rapid translocation of MVP into lipid raft (LR) membrane fractions. Like AHLs, inflammatory stimuli also induce LR-localization of MVP, but the C12 stimulation reprograms (functionalizes) bioactivity of the plasma membrane by recruiting death receptors, their apoptotic adaptors, and caspase-8 into LR. These functionalized membranes control AHL-induced signaling processes, in that MVP adjusts the protein kinase p38 pathway to attenuate programmed cell death. Since MVP is the structural core of large particles termed vaults, our findings suggest a mechanism in which MVP vaults act as sentinels that fine-tune inflammation-activated processes such as apoptotic signaling mediated by immunosurveillance cytokines including tumor necrosis factor-related apoptosis inducing ligand (TRAIL). National Academy of Sciences 2021-03-23 2021-03-15 /pmc/articles/PMC8000436/ /pubmed/33723037 http://dx.doi.org/10.1073/pnas.2012529118 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Rayo, Josep Gregor, Rachel Jacob, Nicholas T. Dandela, Rambabu Dubinsky, Luba Yashkin, Alex Aranovich, Alexander Thangaraj, Manikandan Ernst, Orna Barash, Eran Malitsky, Sergey Florea, Bogdan I. Krom, Bastiaan P. Wiemer, Erik A. C. Kickhoefer, Valerie A. Rome, Leonard H. Mathison, John C. Kaufmann, Gunnar F. Overkleeft, Herman S. Cravatt, Benjamin F. Zor, Tsaffrir Janda, Kim D. Ulevitch, Richard J. Kravchenko, Vladimir V. Meijler, Michael M. Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones |
title | Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones |
title_full | Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones |
title_fullStr | Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones |
title_full_unstemmed | Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones |
title_short | Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones |
title_sort | immunoediting role for major vault protein in apoptotic signaling induced by bacterial n-acyl homoserine lactones |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000436/ https://www.ncbi.nlm.nih.gov/pubmed/33723037 http://dx.doi.org/10.1073/pnas.2012529118 |
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