Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N -acyl homoserine lactones

• DOI: 10.1073/pnas.2012529118
• Publication Date: 2021-03-15T22:06:11Z
• Authors: Josep Rayo; Rachel Gregor; Nicholas T. Jacob; Rambabu Dandela; Luba Dubinsky; Alex Yashkin; Alexander Aranovich; Manikandan Thangaraj; Orna Ernst; Eran Barash; Sergey Malitsky; Bogdan I. Florea; Bastiaan P. Krom; Erik A. C. Wiemer; Valerie A. Kickho...; Leonard H. Rome; John C. Mathison; Gunnar F. Kaufmann; Herman S. Overkleeft; Benjamin F. Cravatt; Tsaffrir Zor; Kim D. Janda; Richard J. Ulevitch; Vladimir V. Kravc...; Michael M. Meijler
• Keywords: Homoserine; Cell Signaling

The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses Pseudomonas aeruginosa Here, we report the use of photoactive probes identify MVP as a target N-(3-oxo-dodecanoyl) homoserine lactone (C12), quorum sensing signal certain proteobacteria P. aeruginosa. A treatment normal cells with C12 or other N-acyl lactones (AHLs) results in rapid translocation into lipid raft (LR) membrane fractions. Like AHLs, stimuli also induce LR-localization MVP, but stimulation reprograms (functionalizes) bioactivity plasma by recruiting death receptors, their apoptotic adaptors, caspase-8 LR. These functionalized membranes control AHL-induced signaling processes, that adjusts kinase p38 pathway attenuate programmed death. Since is structural core large particles termed vaults, our findings suggest mechanism which vaults act sentinels fine-tune inflammation-activated processes such mediated immunosurveillance cytokines tumor necrosis factor-related apoptosis inducing ligand (TRAIL).