Figure 1

Nuclear IKKα-dependent molecular regulations of NF-κB-mediated gene transcription. In response to a variety of stimuli, including proinflammatory cytokines, pathogens, and growth factors, IKKα translocates into the nucleus and bind to DNA in association with CBP to phosphorylate histone H3 at Ser10, CBP at Ser1382/1386, and p65 at S536. Nuclear IKKα also removes repressive HDAC3/SMRT complex from NF-κB-dependent gene expression through phosphorylating SMRT at Ser2410. These events facilitate the formation of transcriptional enhanceosome to increase NF-κB-dependent gene expression. On the other hand, nuclear IKKα also contributes to the termination of NF-κB-mediated gene transcriptions by phosphorylating p65 at Ser536 and PIAS at Ser90 to facilitate the turnover of p65 in response to TNF-α or LPS stimulation.