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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2021
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).
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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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