Figure 4.

Schematic for the main PTMs of NF-κB (p65 subunit) and their functional activity. Three main PTMs of the p65 subunit are methylation, phosphorylation, or acetylation. Methylation is catalyzed by HMTs that utilize SAM as donor of methyl groups, with formation of SAH. K218 and K221 are two main methylated aminoacidic residues. This modification has the functional effect of increasing the transcriptional activity of NF-κB and, by inhibiting S536 residue dephosphorylation, prolonging the activation. Phosphorylation of p65, catalyzed by PKs, is an important PTM for protein stability and transcriptional activity. Two of the indicated residues, S276 and S536, play a role in nuclear import and protein interaction with CBP/p300. Acetylation of NF-κB is important for DNA binding, and transcriptional activity. HAT catalyzes acetylation by using acetyl-CoA, which is mainly produced by ACLY, one of the NF-κB-regulated genes. Three of the main residues that have been acetylated are K218, K221, and K310. Abbreviation: ME: methyl group, Pi: phosphate group, Ac: acetyl group, HMTs: histone-methyltransferases, SAM: S-adenosyl-L-methionine, SAH: S-adenosyl homocysteine, PKs: protein kinases, HATs: histone acetyl transferases, ACLY: ATP-citrate lyase.