Fig. 9: Schematic summary of the study. | Nature Communications

Fig. 9: Schematic summary of the study.

From: Disrupting bile acid metabolism by suppressing Fxr causes hepatocellular carcinoma induced by YAP activation

Fig. 9

a YAP regulation of Fxr activity and BA metabolism. A proposed model for YAP, Fxr, and BAs forms a dynamic regulatory network. YAP activation inhibits Fxr transcriptional activity, causing BA accumulation in hepatocytes by downregulating Bsep expression. Pharmacological activation of Fxr by GW4064 not only curtails BA production and promotes BA exportation but also directly inhibits YAP activity, alleviating tumor formation caused by YAP activation. b Dynamic regulation of YAP and FXR transcriptional activity by P300 and HDAC1. Pharmacological activation of FXR by GW4064 relieves YAP inhibition of FXR by recruiting P300 and inhibiting HDAC1 binding to FXR. Meanwhile, it promotes the repressor function of the DNA-binding YAP-TEAD complex, converting it from a transcriptional activator to a transcriptional repressor.

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