The roles of nuclear IKKα in the regulation of NF-κB-independent gene transcription. Nuclear IKKα enhances Notch-dependent gene transcriptional by phosphorylating and removing co-repressor SMRT from target gene promoters. IKKα also contributes to Notch transcriptional activity through phosphorylating and inactivating FOXA2, which subsequently leads to NUMB suppression. By direct target on transcription factors, nuclear IKKα also increases AP-1, ERα, and E2F-mediated gene transcription. Phosphorylation of SRC3 at Ser857 by nuclear IKKα also contributes to ERα transcriptional activity.