TEA domain family member 3 (TEAD3) (TEAD3)

TEA domain family member 3 (TEAD3) is a transcription factor belonging to the TEA/ATTS domain family and serves as a critical downstream effector of the Hippo signaling pathway. It functions by forming complexes with transcriptional co-activators, most notably 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. TEAD3 is uniquely characterized by its high expression in the placenta and its essential role in embryonic development, particularly in trophoblast differentiation and cardiac lineage commitment. In oncology, TEAD3 is frequently overexpressed in cancers such as ovarian, endometrial, and breast cancer, where it correlates with poor prognosis and promotes tumor progression through the activation of pro-growth gene networks. Conversely, it has been identified as a potential tumor suppressor in prostate and colorectal cancers, highlighting its context-dependent role in different tissue environments. Therapeutic targeting of TEAD3 primarily involves small molecules that either disrupt the TEAD-YAP/TAZ protein-protein interaction or bind to a conserved hydrophobic palmitoylation pocket to inhibit its transcriptional activity. While several pan-TEAD inhibitors are currently in clinical trials for solid tumors, challenges such as potential renal toxicity and the need for isoform specificity remain significant areas of investigation. Additionally, TEAD3 mRNA expression levels serve as important biomarkers for patient selection and monitoring therapeutic efficacy in Hippo-driven malignancies.

Other names

TEF-5DTEF-1ETFR-1TEAD5Transcriptional enhancer factor TEF-5TEAD-3TEA domain transcription factor 3

Inhibition of the TEAD-YAP/TAZ transcriptional complex through disruption of protein-protein interactions, inhibition of TEAD auto-palmitoylation by binding to the conserved lipid pocket, or induction of a cofactor switch to promote binding of transcriptional repressors like VGLL4.