TEA domain transcription factor 4 (TEAD4) (TEAD4)

TEA domain transcription factor 4 (TEAD4), also known as Transcriptional enhancer factor TEF-3, is a member of the TEA domain family of transcription factors and a primary nuclear effector of the Hippo signaling pathway [1, 6]. It functions by binding to DNA at M-CAT motifs and recruiting transcriptional co-activators, most notably Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-binding motif (TAZ), to drive the expression of genes involved in cell proliferation, survival, and epithelial-mesenchymal transition [1, 2]. While essential for embryonic development—particularly in trophoblast lineage determination—TEAD4 is frequently overexpressed in various human cancers, including breast, liver, and lung malignancies, where it promotes tumorigenesis, metastasis, and resistance to chemotherapy [3, 4, 16]. In the context of oncology, TEAD4 has emerged as a high-priority therapeutic target; its activity can be modulated by small molecules that disrupt its interaction with YAP/TAZ or target its unique palmitoylation pocket [1, 2, 13]. Beyond its role in cancer, TEAD4 is involved in muscle-specific gene expression and angiogenesis, highlighting its broader biological significance in regenerative medicine and cardiovascular health [7, 9, 22]. Current drug development efforts are focused on potent, selective TEAD inhibitors that aim to overcome the challenges of targeting transcription factors by exploiting allosteric binding sites [4, 13].

Other names

Transcriptional enhancer factor TEF-3TEF-3RTEF-1Related transcription enhancer factor 1TCF13L1EFTR-2hRTEF-1B

Inhibition of the TEAD-YAP/TAZ protein-protein interaction and allosteric inhibition through binding to the conserved TEAD palmitoylation pocket.