Fig. 2.

A simplified illustration of YAP/TAZ and glycolysis. (a). Glycolysis upregulates the activity of PFK1 (phosphofructokinase) to promote YAP/TAZ transcriptional cooperation with TEAD factors, and form a PFK1-TEAD1-YAP/TAZ complex in cells nucleus. (b). Glycolysis activates YAP through the HBP (hexosamine biosynthesis pathway). YAP is O-GlcNAcylated by OGT (O-linked b-N-acetylglucosamine transferase). O-GlcNAcylation of YAP promotes its nuclear translocation and transcriptional activity. (c). MG (Methylglyoxal), a side-product of glycolysis, promotes YAP transcriptional cooperation with TEAD factors by reducing the binding of HSP90 and LATS1 and inhibiting LATS1 activity. (d). YAP-TEAD binds with the GLUT3 promoter to directly regulate the transcription of GLUT3 and then promotes glycolysis in tumor cells. (e). FOXC2 (forkhead box protein C2) interacts with YAP and TEAD in cells nucleus to activate YAP, and then the activation of YAP upregulates the expression of HK2 to promote cells glycolysis. (f) YAP-TEAD directly binds with the two site (GGAATT/GGAATC) in the promoter region of lncRNA BCAR4 to upregulate the expression and transcriptional activity of HK2 and PFKFB3 to promote cells glycolysis