The YAP and TAZ transcription co-activators: Key downstream effectors of the mammalian Hippo pathway

► The Hippo pathway plays a key role in organ size control and dysregulation of the pathway contributes to tumorigenesis. ► The YAP/TAZ transcription co-activators are the major downstream effectors of the Hippo pathway. ► YAP/TAZ are phosphorylated and inhibited by the Lats kinase of the Hippo pathway. ► The TEAD family proteins are the major target transcription factors mediating gene expression by YAP/TAZ. The Hippo signaling pathway was initially defined by genetic studies in Drosophila to regulate tissue growth and organ size [1,2]. This pathway is highly conserved in mammals and dysregulation of the Hippo pathway has been implicated in human cancer. Although the exact extracellular signal that controls the Hippo pathway is currently unknown, compelling evidence supports a critical role of the Hippo pathway in cell contact inhibition, which is a property commonly lost in cancer cells. Many molecules, such as the merlin tumor suppressor protein, have been identified as regulating the activity of the core Hippo pathway components [1,2]. Acting downstream are two key transcription co-activators, YAP and TAZ, which mediate the major gene regulation and biological functions of the Hippo pathway. This article will focus on the physiological function and molecular regulation of YAP/TAZ and its Drosophila homolog Yki.