The regulation and function of YAP transcription co-activator

Abstract

The Hippo pathway was initially identified in Drosophila by genetic mosaic screens for tumor suppressor genes. Researches indicated that the Hippo pathway is a key regulator of organ size and is conserved during evolution. Furthermore, studies of mouse models and clinical samples demonstrated the importance of Hippo pathway dysregulation in human cancer development. In addition, the Hippo pathway contributes to progenitor cell and stem cell self-renewal and is thus involved in tissue regeneration. In the Hippo pathway, MST1/2 kinases together with the adaptor protein SAV phosphorylate LATS1/2 kinases. Interaction with an adaptor protein MOB is also important for LATS1/2 activation. Activated LATS1/2 in turn phosphorylate and inhibit Yes-associated protein (YAP). YAP is a key downstream effector of the Hippo pathway, and is a transcriptional co-activator that mainly interacts with TEAD family transcription factors to promote gene expression. Alteration of gene expression by YAP leads to cell proliferation, apoptosis evasion, and also stem cell amplification. In this review, we mainly focus on YAP, discussing its regulation and mechanisms of action in the context of organ size control, tissue regeneration and tumorigenesis.

Keywords: Hippo; YAP; apoptosis; cancer; organ size; proliferation.