Aug 2026· Cold Spring Harbor Perspectives in Biology· pp. a041913· 0 citations
Medicine
TL;DR
This review summarizes recent advances in how NF2 regulates YAP/TAZ and AMOT functions, focusing on their roles in tumor formation, metastasis, and angiogenesis.
Abstract
The Hippo pathway is a central regulator of tissue homeostasis, organ growth, and tumorigenesis. NF2 (Neurofibromin 2, also known as Merlin) functions as a pivotal upstream component that integrates biochemical and mechanical cues to restrain the activity of the transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), thereby limiting cell proliferation. In addition, NF2 regulates members of the Motin family proteins (AMOT, AMOTL1, and AMOTL2) through ubiquitin-mediated turnover to modulate YAP/TAZ signaling output. Moreover, NF2 controls AMOT proteolytic processing to reorganize the actin cytoskeleton, thereby influencing cell motility. Through these mechanisms, NF2 establishes a multilayered regulatory system that coordinates cell proliferation and cell migration. This review summarizes recent advances in how NF2 regulates YAP/TAZ and AMOT functions, focusing on their roles in tumor formation, metastasis, and angiogenesis.
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.
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