YAP/TAZ: An epitome of tumorigenesis

Abstract

Mounting evidence has demonstrated that the transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are the main effectors of the Hippo signal transduction pathway that is involved in multiple layered events in tumorigenesis. The role of YAP/TAZ in cancer development is critical in a context dependent manner. Overexpression of YAP/TAZ induces cell proliferation and is elevated in various cancers and many other malignancies. On the other hand, studies have shown YAP binds p73 to activate PML transcription in response to DNA damage and generate a DNA-damage-induced feedback loop. Intriguingly, at the genomic level, YAP/TAZ genes are rarely mutated in cancer, except in specific tumors. The central role of YAP/TAZ in driving tumorigenesis is attributed through diverse mechanisms, such as regulatory kinases, cellular mechano-transduction, epigenetic modification/alterations, post-translational modifications, protein -protein interaction and nucleo-cytoplasmic export import. The complex interplay among feedback loops and crosstalk between various signaling pathways portrays the dynamic nature of YAP/TAZ. Thus, a comprehensive understanding of how posttranslational modifications and nucleo-cytoplasmic traffic of YAP/TAZ dynamically regulate and control each other holds great promise for selectively targeting YAP/TAZ import and export for drug therapy.

Keywords: Hippo pathway; Post translational modifications (PTM); Transcriptional coactivator with PDZ-Binding motif (TAZ); Tumorigenesis; Yes-associated protein (YAP).