Regulation of the Hippo Pathway Transcription Factor TEAD

The TEAD transcription factor family is best known for transcriptional output of the Hippo signaling pathway and has been implicated in processes such as development, cell growth and proliferation, tissue homeostasis, and regeneration. Our understanding of the functional importance of TEADs has increased dramatically since its initial discovery three decades ago. The majority of our knowledge of TEADs is in the context of Hippo signaling as nuclear DNA-binding proteins passively activated by Yes-associated protein (YAP) and transcriptional activator with PDZ-binding domain (TAZ), transcription coactivators downstream of the Hippo pathway. However, recent studies suggest that TEAD itself is actively regulated. Here, we highlight evidence demonstrating Hippo-independent regulation of TEADs and the potential impacts these studies may have on new cancer therapeutics. The TEAD family of transcription factors (TEAD1–4) is best studied in the context of Hippo signaling. TEADs are the primary transcription factors for the YAP/TAZ transcription coactivators of the Hippo pathway. TEADs play an important role in development, tissue homeostasis, and tumorigenesis through regulation of processes such as cell growth and proliferation, differentiation, and survival. These processes are largely thought to be regulated by binding of YAP/TAZ. Recent studies have uncovered new Hippo-independent mechanisms of TEAD regulation including post-translational modifications and changes in subcellular localization.