Fig. 4

A simplified illustration of YAP/TAZ and mevalonate. HMG CoA produces mevalonate through the activity of the HMG CoA reductase (HMGCR). Geranylgeranyl pyrophosphate (GGPP), the intermediate of mevalonate metabolism, activates RHO to promote YAP/TAZ transcriptional cooperation with TEAD factors in cells nucleus. Then YAP/TAZ-TEAD binds the specific sites in the RHAMM promoter to play the function role of transcription regulation. The transcription of HMG CoA reductase (HMGCR) also can be inhibited by Statins or activated by SREBP transcription factors, which can be upregualted by mutant p53. This explains why some small-molecule inhibitors such as statins could inhibit the nuclear localization and transcriptional activity of YAP/TAZ