FIGURE 1.

Regulatory pathways in cell proliferation and differentiation involving Yes‐associated protein (YAP). (1) YAP is phosphorylated at high cell density and low mechanical tension. (2) The switch between the YAP/TEAD (transcriptional enhanced associate domain) and YAP/RUNX3 complexes—which promotes and inhibits cell proliferation, respectively—regulates the cell cycle. After entering the nucleus, YAP competes with VGLL4 for binding to the transcription factor TEAD, thereby maintaining cell proliferation. ¹⁸ (3) The YAP/TEAD complex activates WNT16/GSK3β/β‐catenin to bind to TCF/LEF (transcription factor/ lymphoid enhancer binding factor), promoting cell proliferation. The integrin/Src and EGFR/PI3K pathways promote YAP nuclear localization; B‐plexin phosphorylates YAP; Hedgehog (HH) signaling activates YAP; and nuclear YAP binds to β‐catenin to activate HH signaling. YAP also binds to p73, increasing p53AIP1 and Bax expression, while the upregulation of DR5 and PUMA promotes cell apoptosis. YAP increases the expression of Plau and Tgfbr3 to enhance keratinocyte proliferation.