Once in the nucleus, activated NF-κB undergoes a series of posttranslational modifications, including phosphorylation, acetylation, and methylation. These modifications regulate both the strength and duration of NF-κB activity. RelA/p65 is directly phosphorylated by cAMP- dependent protein kinase (PKA) at Ser276, casein kinase II (CKII) at Ser529, and IKK at Ser536 [20, 21]. RelA dephosphorylation by protein phosphatase 2A (PP2A) has been reported to decrease NF-κB activity [22]. RelA is subject to inducible acetylation by p300/CBP, and acetylated RelA interacts weakly, if at all, with IκBα [23, 24], but maintains its nuclear localization and NF-κB transcriptional response. RelA is also subject to methylation by lysine methyltransferase Set9 (also called Set7 or KMT7) at Lys314/315 [25].
