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The proapoptotic function of Daxx by transcriptional repression of NF-kB activity was investigated. Overexpression of Daxx in human 293 cells repressed the NF-kB activity in the presence of TNFα stimulation. Daxx repressed the binding of NF-kB to DNA and TNFα-induced NF-kB-dependent reporter gene expression. However, RNA interference depletion of Daxx enhanced NF-kB activity. We found Daxx interacted with IkBα and inhibited the phosphorylation and degradation of IkBα in TNFα-stimulated cells. This study suggests that the proapoptotic function of Daxx during TNFα-induced apoptosis is potentiated by the increased stability of IkBα after its binding with Daxx and subsequent repression of transactivation of NF-kB which inhibits apoptosis by transactivating antiapoptotic genes.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]