Figure 1.

Hippo pathway and its physiological and oncogenic roles. The Hippo pathway is comprised of serine/threonine kinases activated by a phosphorylation cascade, the core of which starts with MST1/5, which activates LATS1/2 and NDR1/2. The latter two regulate by phosphorylation the activation of the effector proteins YAP1 and TAZ. When phosphorylated, YAP1 and TAZ are degraded by the proteasome and/or sequestered in the cytoplasm. (A) In a physiological context, YAP1 and TAZ are found in an equilibrium of active and inactive forms that regulate the transcription of various target genes such as CTFG, ANKDR1 and CYR61. (B) In cancer, YAP1 and/or TAZ are often found in hyperactive states due to reduced regulation of Hippo kinases, thereby playing an oncogenic role. MST1/5, mammalian sterile 20-like kinase; LATS1/2, large tumour suppressor 1/2; NDR1/2, nuclear dbf2-related kinase; YAP1, yes-associated protein 1; TAZ, transcriptional coactivator with a PDZ-binding domain; TEAD, TEA DNA-binding protein; TAOK, Thousand and one amino-acid kinase.