Fig. 5. Smad3-recruited HDAC2 induces NF-κB deacetylation at K310.
TGFβ1 signaling decreases MUC5AC expression transcriptionally in NCI-H292 cells. Steps ① and ②: TGFβ1-binding to TGFβ receptors activates Smad3 by phosphorylation. Steps ③ and ④: Activated Smad3 binds to HDAC2 and makes a protein complex (Smad3/HDAC2 complex), which translocates to the cell nucleus. Step ⑤: Activated Smad3 in the cell nucleus binds to the promoter region of MUC5AC and reduces its expression. Step ⑥: Smad3/HDAC2 complex induces the deacetylation of Ac-NF-κB at K310, thereby reducing the transcriptional activity of NF-κB. Deacetylation of Ac-NF-κB at K310 is considerably restored by adding a Smad3 inhibitor (SIS3). Step ⑦: This study is undefined whether the deacetylation of NF-κB at K310 is mediated by HDAC2 directly or indirectly.
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