Hippo signaling regulates the nuclear behavior and DNA binding times of YAP and TEAD to control transcription

B Kroeger; SA Manning; V Mohan; J Lou; G Sun; S Lamont; AJ McCann; M Francois; JM Polo; E Hinde; KF Harvey

Journal article

Hippo signaling regulates the nuclear behavior and DNA binding times of YAP and TEAD to control transcription

B Kroeger, SA Manning, V Mohan, J Lou, G Sun, S Lamont, AJ McCann, M Francois, JM Polo, E Hinde, KF Harvey

Science Advances | Published : 2025

DOI: 10.1126/sciadv.adw4974

Abstract

Over the past two decades, genetic and proteomic screens have identified the Hippo pathway as a complex signaling network that controls tissue growth and human cancer. Despite these advances, our understanding of how Hippo signaling regulates transcription is less clear. To address this, we used live microscopy to study the nuclear behavior of the major Hippo pathway transcription effectors, YAP and TEADs. We reveal that TEADs are a major determinant of YAP DNA binding and nuclear mobility, while YAP minorly influences TEADs. YAP and TEAD1 associate with DNA for longer periods in cells with intrinsically low Hippo pathway activity and upon acute Hippo pathway perturbation. TEAD1 binds the ge..

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