Aug 2026· Cold Spring Harbor Perspectives in Biology· 0 citations
Medicine
TL;DR
This review provides an updated overview of this transcriptional module within the Hippo pathway, discusses how it modulates gene transcription to contribute to development and disease, and proposes outstanding questions that warrant further investigation in future studies.
Abstract
The Hippo pathway regulates cell proliferation, cell death, and differentiation, and thus plays a key role in organ size control and tissue homeostasis throughout animal development and adult life. Aberrant Hippo signaling is a key driver of human cancer, developmental disorders, other pathological conditions, and aging. Yes-associated protein (YAP) and its paralog, transcriptional coactivator with PDZ-binding motif (TAZ), are two transcriptional coactivators that mediate the major functions of the Hippo pathway by binding to specific transcription factors, such as members of the transcriptional enhanced associate domain (TEAD) family. In this review, we provide an updated overview of this transcriptional module within the Hippo pathway, discuss how it modulates gene transcription to contribute to development and disease, and propose outstanding questions that warrant further investigation in future studies.
A unified mechanistic framework by which the level of YAP/TAZ activity determines enhancer landscapes that favor either differentiated or progenitor-like cellular states is proposed, providing a potential basis for applications to regenerative medicine and therapeutic interventions.
Ju-Gyeong Kang, Taejun Seol, Younghoon Kim et al.· Cold Spring Harbor Perspecti...· 0 citations
Transcriptional-enhanced associate (TEA)/transcriptional enhanced factor (TEF) domain transcription factors (TEAD1-4) regulate the transcriptional output of Hippo signaling by interacting with the coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) and play a crucial r...
Xu Wu, J. Mao· Cold Spring Harbor Perspecti...· 0 citations
The spatiotemporal control of core pathway components in murine and human lungs is reviewed, highlighting how YAP and TAZ integrate mechanical and molecular cues to govern epithelial patterning, mesenchymal function, vascular integrity, and stem cell behavior.
K. Kontodimas, X. Varelas· Cold Spring Harbor Perspecti...· 0 citations
This review summarizes recent advances in how NF2 regulates YAP/TAZ and AMOT functions, focusing on their roles in tumor formation, metastasis, and angiogenesis.
Yu Wang, Fa-Xing Yu· Cold Spring Harbor Perspecti...· 0 citations
This review delineates the biological functions of the Hippo–YAP/TAZ–TEAD axis and integrate its pathway physiology with the structural basis of druggability, centered on the Ω‐loop surface pocket and the buried palmitoylation‐binding pocket of TEAD, whose distinct geometries dictate the pharmacophoric requirements, pa...
Small-molecule NUAK inhibitors are in development, several of which have been shown to reactivate Hippo signaling, restore YAP/TAZ cytoplasmic retention, and suppress aberrant cancer cell proliferation and fibrosis.
Youchen Song, Liliana Attisano· Cold Spring Harbor Perspecti...· 0 citations
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