Core Components of the Hippo Pathway

The Hippo signaling pathway is an evolutionarily conserved regulatory module that orchestrates a wide range of cellular and physiological processes. It integrates diverse upstream signals and through a sequential kinase cascade to control transcription. The large tumor suppressor (LATS) kinase phosphorylates Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) to induce their cytoplasmic localization and inactivation. Once localized in the nucleus, the unphosphorylated YAP/TAZ serve as transcriptional coactivators and interact with the TEA domain (TEAD) DNA-binding transcription factors to drive the expression of target genes that are involved in cell proliferation, apoptosis, differentiation, extracellular matrix remodeling, cytoskeleton organization, and organ size control. The precise and robust transmission of phosphorylation signals within the pathway is ensured by the coordinated action of multiple core components. In this work, we focus on the molecular module underlying the regulation of the Hippo pathway, with an emphasis on how the structural and functional properties of its core proteins contribute to the faithful relay of phosphorylation signal to transcriptional regulation of downstream target genes.