Figure 1.

Energy stress regulates the Hippo-YAP pathway. Both AMPK and LATS kinases are activated under energy stress, and once activated phosphorylate YAP at several residues, contributing to the inhibition of YAP transactivation activity. Release from energy stress leads to translocation of YAP into the nucleus, where it forms a complex with TEAD to initiate downstream gene transcription. In addition, a glycolysis enzyme PFK1 has recently been shown to interact with TEAD and maintain the YAP-TEAD complex in the nucleus. The active YAP-TEAD complex promotes cell proliferation, anti-apoptosis, and glycolysis, in part by upregulating GLUT3 and possibly also HK2.