TEA domain family member (TEAD) (TEAD)

The TEA domain family member (TEAD) proteins, historically referred to as Transcriptional Enhancer Factors (TEF), are a group of four transcription factors (TEAD1-4) that serve as the primary nuclear effectors of the Hippo signaling pathway (Panciera et al., 2017; UniProt Consortium, 2024). These proteins lack intrinsic transcriptional activation domains and must recruit co-activators, specifically Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-binding motif (TAZ), to regulate the expression of genes involved in cell proliferation, survival, and organ size control (Zhou et al., 2023). In various malignancies, such as malignant mesothelioma and NF2-deficient cancers, the Hippo pathway is frequently dysregulated, resulting in the constitutive activation of the TEAD-YAP/TAZ complex and the promotion of oncogenic phenotypes (Noland et al., 2016). Consequently, TEAD has emerged as a high-priority therapeutic target in oncology. Current pharmacological strategies involve small-molecule inhibitors that target a conserved internal palmitoylation pocket within the TEAD protein, which is necessary for its stability and its ability to bind YAP/TAZ (Ikena Oncology, 2024; Vivace Therapeutics, 2024). Clinical trials are currently evaluating several TEAD inhibitors, such as IK-930 and VT3989, for their efficacy in treating Hippo-pathway-driven solid tumors (ClinicalTrials.gov, 2024).

Other names

Transcriptional enhancer factorTEFTEA domain-containing transcription factorTEAD1TEAD2TEAD3TEAD4TEF-1TEF-3TEF-4TEF-5

Small-molecule inhibition of TEAD auto-palmitoylation, which destabilizes the protein and prevents its interaction with the transcriptional co-activators YAP and TAZ (Noland et al., 2016; Zhou et al., 2023).