Figure 7: Model for persistent activation of NF-κB by PHF20.
From: PHF20 regulates NF-κB signalling by disrupting recruitment of PP2A to p65
It is known from the literature that NSD1 targets p65 for methylation on Lys218 and Lys221 residue functions to stabilize the formation of p65–DNA complex. p65 is also phosphorylated on Ser536 by various kinases, including IKKα, IKKβ or RSK1, which enhances its transactivation potential through recruiting histone acetyltransferase such as CBP and p300. (a) The recruitment of PP2A into phosphorylated p65 ensures that the NF-κB response maintains tight control during its activation to achieve proper termination. (b) Gain of PHF20 recognizes p65 methylated at Lys221, and associates with p65. Such association may block a docking site for recruitment of PP2A into p65 that leads to persistent NF-κB response.
