Phosphorylation of NF-κB p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300
Phosphorylation of NF-κB p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300
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DOI：
10.1016/s1097-2765(00)80066-0
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发表时间：
1998-04-01
期刊：
影响因子：
16
通讯作者：
Ghosh, S
中科院分区：
文献类型：
--
作者：
Zhong, HH;Voll, RE;Ghosh, S
NF-κ B B的转录活性在其p65亚基在丝氨酸276上被蛋白激酶A（PKA）磷酸化后被刺激。转录辅激活因子CBP/p300通过两个位点与NF-κ B p65结合，一个是与未磷酸化p65的C-末端区域相互作用的N-末端结构域，另一个是仅与丝氨酸276上磷酸化的p65相互作用的第二个结构域。通过pS5的C-末端区域对N末端的分子内掩蔽，在未磷酸化的p65中阻断了对这两个位点的可及性。PKA的磷酸化既削弱了p65的N-和C-末端区域之间的相互作用，又创造了一个与CBP/p300相互作用的额外位点。因此，PKA通过调节NF-κ B与CBP/p300的相互作用来调节NF-κ B的转录活性。
The transcriptional activity of NF-kappa B is stimulated upon phosphorylation of its p65 subunit on serine 276 by protein kinase A (PKA). The transcriptional coactivator CBP/p300 associates with NF-kappa B p65 through two sites, an N-terminal domain that interacts with the C-terminal region of unphosphorylated p65, and a second domain that only interacts with p65 phosphorylated on serine 276. Accessibility to both sites is blocked in unphosphorylated p65 through an intramolecular masking of the N terminus by the C-terminal region of pS5. Phosphorylation by PKA both weakens the interaction between the N- and C-terminal regions of p65 and creates an additional site for interaction with CBP/p300. Therefore, PKA regulates the transcriptional activity of NF-kappa B by modulating its interaction with CBP/p300.