Taken together, this identification of Smac mimetic-stimulated, NF-κB-dependent upregulation of IFNβ and engagement of proapoptotic IFN signaling pathways provides novel insights into the molecular mechanisms that are responsible for Smac mimetic-mediated sensitization of glioblastoma cells to TMZ-induced cell death. Here, NFKB1 is linked to glioblastoma.