Hippo pathway signaling and YAP/TAZ
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The Hippo-independent regulations and functions of TEADs, as well as the role of the TEAD-VGLL complex in development and disease, shedding light on therapeutic strategies of targeting the TEAD-VGLL complex are discussed.
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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 role in animal development and tumorigenesis.Much of the regulation of the TEAD-YAP/TAZ complex is through the regulation of nuclear translocation and degradation of YAP/TAZ by the upstream Hippo pathway regulators.However, TEADs undergo several posttranslational modifications, which are mostly independent of upstream Hippo pathway components.Alternative splicing of TEAD1 has also been reported to modulate TEAD activities posttranscriptionally.In addition, TEADs can bind to Vestigial-like (VGLL) proteins, which regulate distinct transcription programs that influence tumor growth, immunity, and development.VGLL1-3 may act as transcriptional activators or repressors, while VGLL4 functions primarily as a repressor by competing with YAP/TAZ for TEAD binding.Here, we discuss the Hippo-independent regulations and functions of TEADs, as well as the role of the TEAD-VGLL complex in development and disease, shedding light on therapeutic strategies of targeting the TEAD-VGLL complex.
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@article{Wu2026Hippo,
title = {Hippo-Independent Regulation and Functions of the TEAD and TEAD–VGLL Complexes},
author = {Xu Wu and Junhao Mao},
journal = {Cold Spring Harbor Perspectives in Biology},
year = {2026},
doi = {10.1101/cshperspect.a041920},
url = {https://doi.org/10.1101/cshperspect.a041920}
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