Daxx mediates activation-induced cell death in microglia by triggering MST1 signalling

Hee Jae Yun, Je Hyun Yoon, Jae Keun Lee, Kyung Tae Noh, Kyoung Wan Yoon, Sang Phil Oh, Hyun Jung Oh, Ji Soo Chae, Sang Gil Hwang, Eun Hee Kim, Gerd G. Maul, Dae Sik Lim, Eui Ju Choi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Microglia, the resident macrophages of the mammalian central nervous system, migrate to sites of tissue damage or infection and become activated. Although the persistent secretion of inflammatory mediators by the activated cells contributes to the pathogenesis of various neurological disorders, most activated microglia eventually undergo apoptosis through the process of activation-induced cell death (AICD). The molecular mechanism of AICD, however, has remained unclear. Here, we show that Daxx and mammalian Ste20-like kinase-1 (MST1) mediate apoptosis elicited by interferon-Î 3 (IFN-Î 3) in microglia. IFN-Î 3 upregulated the expression of Daxx, which in turn mediated the homodimerization, activation, and nuclear translocation of MST1 and apoptosis in microglial cells. Depletion of Daxx or MST1 by RNA interference also attenuated IFN-Î 3-induced cell death in primary rat microglia. Furthermore, the extent of IFN-Î 3-induced death of microglia in the brain of MST1-null mice was significantly reduced compared with that apparent in wild-type mice. Our results thus highlight new functions of Daxx and MST1 that they are the key mediators of microglial cell death initiated by the proinflammatory cytokine IFN-Î 3.

Original languageEnglish
Pages (from-to)2465-2476
Number of pages12
JournalEMBO Journal
Volume30
Issue number12
DOIs
Publication statusPublished - 2011 May

Keywords

  • Daxx
  • MST1
  • cell death
  • interferon-g
  • microglia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Daxx mediates activation-induced cell death in microglia by triggering MST1 signalling'. Together they form a unique fingerprint.

  • Cite this

    Yun, H. J., Yoon, J. H., Lee, J. K., Noh, K. T., Yoon, K. W., Oh, S. P., Oh, H. J., Chae, J. S., Hwang, S. G., Kim, E. H., Maul, G. G., Lim, D. S., & Choi, E. J. (2011). Daxx mediates activation-induced cell death in microglia by triggering MST1 signalling. EMBO Journal, 30(12), 2465-2476. https://doi.org/10.1038/emboj.2011.152