APA
Click to copy
Rayo, J., Gregor, R., Jacob, N. T., Dandela, R., Dubinsky, L., Yashkin, A., … Meijler, M. (2021). Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones. Proceedings of the National Academy of Sciences.
Chicago/Turabian
Click to copy
Rayo, Josep, R. Gregor, Nicholas T. Jacob, R. Dandela, Luba Dubinsky, A. Yashkin, A. Aranovich, et al. “Immunoediting Role for Major Vault Protein in Apoptotic Signaling Induced by Bacterial N-Acyl Homoserine Lactones.” Proceedings of the National Academy of Sciences (2021).
MLA
Click to copy
Rayo, Josep, et al. “Immunoediting Role for Major Vault Protein in Apoptotic Signaling Induced by Bacterial N-Acyl Homoserine Lactones.” Proceedings of the National Academy of Sciences, 2021.
BibTeX Click to copy
@article{josep2021a,
title = {Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones},
year = {2021},
journal = {Proceedings of the National Academy of Sciences},
author = {Rayo, Josep and Gregor, R. and Jacob, Nicholas T. and Dandela, R. and Dubinsky, Luba and Yashkin, A. and Aranovich, A. and Thangaraj, Manikandan and Ernst, Orna and Barash, E. and Malitsky, S. and Florea, B. and Krom, B. P. and Wiemer, E. and Kickhoefer, V. and Rome, L. and Mathison, J. and Kaufmann, G. and Overkleeft, H. and Cravatt, B. and Zor, T. and Janda, K. and Ulevitch, R. and Kravchenko, V. and Meijler, M.}
}
Significance It has become clear that our immune system can significantly inhibit the growth of cancer cells, in a process that has been coined “cancer immunoediting.” Based on this model, if the programmed cell death (apoptosis) mediated through immunosurveillance processes is not successful, the tumor cells may enter an equilibrium phase where they are either maintained or “edited” immunologically, leading to populations of tumor variants in the escape phase. Microbial factors have been found to affect cancer immunoediting. In this study we have identified a central player in these processes, called the major vault protein (MVP). Binding of certain bacterial signaling molecules to MVP strongly modulates apoptotic signaling, provoking new ideas and avenues to understand human-bacterial relationships and fight cancer. 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).