RGD Reference Report - Daxx mediates activation-induced cell death in microglia by triggering MST1 signalling. - Rat Genome Database

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

Authors: Yun, HJ  Yoon, JH  Lee, JK  Noh, KT  Yoon, KW  Oh, SP  Oh, HJ  Chae, JS  Hwang, SG  Kim, EH  Maul, GG  Lim, DS  Choi, EJ 
Citation: Yun HJ, etal., EMBO J. 2011 May 13;30(12):2465-76. doi: 10.1038/emboj.2011.152.
RGD ID: 9587767
Pubmed: PMID:21572393   (View Abstract at PubMed)
PMCID: PMC3116283   (View Article at PubMed Central)
DOI: DOI:10.1038/emboj.2011.152   (Journal Full-text)

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-gamma (IFN-gamma) in microglia. IFN-gamma 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-gamma-induced cell death in primary rat microglia. Furthermore, the extent of IFN-gamma-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-gamma.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Mst1Rathistone kinase activity  IDA  RGD 
SlkRathistone kinase activity  IDA  RGD 
SlkRatprotein binding  IPIDaxx (Rattus norvegicus) RGD 
DaxxRatprotein kinase binding  IPISlk (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Daxx  (death-domain associated protein)
Mst1  (macrophage stimulating 1)
Slk  (STE20-like kinase)


Additional Information