YAP-VGLL4 antagonism defines the major physiological function of the Hippo signaling effector YAP.

ABSTRACT: The Hippo-YAP signaling pathway plays a critical role in development, homeostasis, regeneration, and tumorigenesis by converging on YAP, a coactivator for the TEAD family DNA-binding transcription factors, to regulate downstream transcription programs. Given its pivotal role as the nuclear effector of the Hippo pathway, YAP is indispensable in multiple developmental and tissue contexts. Here we report that the essentiality of YAP in liver and lung development can be genetically bypassed by simultaneous inactivation of the TEAD corepressor VGLL4. This striking antagonistic epistasis suggests that the major physiological function of YAP is to antagonize VGLL4. We further show that the YAP-VGLL4 antagonism plays a widespread role in regulating Hippo pathway output beyond normal development, a

SUBMITTER: Cai J 

PROVIDER: S-EPMC9851404 | biostudies-literature | 2022 Nov-Dec 1

REPOSITORIES: biostudies-literature