Caspase-8 controls the secretion of inflammatory lysyl-tRNA synthetase in exosomes from cancer cells

Sang Bum Kim, Hye Rim Kim, Min Chul Park, Seongmin Cho, Peter C. Goughnour, Daeyoung Han, Ina Yoon, Youn Ha Kim, Taehee Kang, Eunjoo Song, Pilhan Kim, Hyosun Choi, Ji Young Mun, Chihong Song, Sangmin Lee, Hyun Suk Jung, Sunghoon Kim

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Abstract

Aminoacyl-tRNA synthetases (ARSs), enzymes that normally control protein synthesis, can be secreted and have different activities in the extracellular space, but the mechanism of their secretion is not understood. This study describes the secretion route of the ARS lysyl-tRNA synthetase (KRS) and how this process is regulated by caspase activity, which has been implicated in the unconventional secretion of other proteins. We show that KRS is secreted from colorectal carcinoma cells within the lumen of exosomes that can trigger an inflammatory response. Caspase-8 cleaved the N-terminal of KRS, thus exposing a PDZ-binding motif located in the C terminus of KRS. Syntenin bound to the exposed PDZ-binding motif of KRS and facilitated the exosomic secretion of KRS dissociated from the multi-tRNA synthetase complex. KRScontaining exosomes released by cancer cells induced macrophage migration, and their secretion of TNF-α and cleaved KRS made a significant contribution to these activities, which suggests a novel mechanism by which caspase-8 may promote inflammation.

Original languageEnglish
Pages (from-to)2201-2216
Number of pages16
JournalJournal of Cell Biology
Volume216
Issue number7
DOIs
Publication statusPublished - 2017 Jul 1

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All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Kim, S. B., Kim, H. R., Park, M. C., Cho, S., Goughnour, P. C., Han, D., Yoon, I., Kim, Y. H., Kang, T., Song, E., Kim, P., Choi, H., Mun, J. Y., Song, C., Lee, S., Jung, H. S., & Kim, S. (2017). Caspase-8 controls the secretion of inflammatory lysyl-tRNA synthetase in exosomes from cancer cells. Journal of Cell Biology, 216(7), 2201-2216. https://doi.org/10.1083/jcb.201605118