The mammalian Hippo pathway: regulation and function of YAP1 and TAZ

Manami Kodaka, Yutaka Hata

The Hippo pathway was originally identified as the signaling that controls organ size in Drosophila, with the core architecture conserved in mammals. In the mammalian Hippo pathway, mammalian Ste20-like kinases (MST1/2) and large tumor suppressor kinases (LATS1/2) regulate transcriptional co-activators, Yes-associated protein (YAP1) and Transcriptional co-activator with a PDZ-binding motif (TAZ). The Hippo pathway was initially thought to be quite straightforward; however, the identification of additional components has revealed its inherent complexity. Regulation of YAP1 and TAZ is not always dependent on MST1/2 and LATS1/2. MST1/2 and LATS1/2 play various YAP1/TAZ-independent roles, while YAP1 and TAZ cross-talk with other signaling pathways. In this review we focus on YAP1 and TAZ and discuss their regulation, function, and the consequences of their dysregulation.