TEA domain transcription factor 3 (TEAD3) (TEAD3)

TEA domain transcription factor 3 (TEAD3), also known as TEAD5 or TEF-5, is a member of the TEA domain family of transcription factors that serve as the primary nuclear effectors of the Hippo signaling pathway [1.1.1, 1.4.2]. It contains a highly conserved N-terminal TEA DNA-binding domain and a C-terminal protein-binding domain that interacts with transcriptional coactivators, most notably YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) [1.1.1, 1.4.4]. TEAD3 is essential for regulating genes involved in cell proliferation, survival, and organ size control, and it plays a specialized role in placental development and cardiac lineage commitment [1.2.2, 1.3.1]. In many human cancers, the Hippo pathway is dysregulated, leading to the hyperactivation of the YAP/TAZ-TEAD complex, which drives tumorigenesis, metastasis, and drug resistance [1.1.1, 1.2.3]. Consequently, TEAD3 and its family members have emerged as attractive therapeutic targets, with drug development efforts focusing on small molecules that either disrupt the YAP/TAZ-TEAD interaction or inhibit TEAD auto-palmitoylation, a post-translational modification required for its stability and activity [1.1.1, 1.2.3]. Most current therapeutic candidates are pan-TEAD inhibitors that target the conserved palmitoylation pocket across all four family members [1.1.1, 1.2.3].

Other names

TEAD5TEF-5DTEF-1ETFR-1Transcriptional enhancer factor 5TEA domain family member 3TEA domain family member 5

Inhibition of TEAD transcriptional activity through disruption of the YAP/TAZ-TEAD protein-protein interaction or inhibition of the TEAD auto-palmitoylation pocket [1.1.1, 1.2.3].