TEA domain family member 3 (TEAD3)

TEA domain family member 3 (TEAD3), also known as Transcriptional enhancer factor TEF-5, is a member of the TEAD family of transcription factors that serve as the primary nuclear effectors of the Hippo signaling pathway (1, 9). TEAD3 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 (1, 4). In many cancers, the Hippo pathway is dysregulated, leading to the hyperactivation of the YAP/TAZ-TEAD complex and the subsequent transcription of oncogenic targets such as CTGF and CYR61 (4, 7). Consequently, TEAD3 is a significant therapeutic target in oncology, particularly for tumors characterized by NF2 mutations or YAP/TAZ overexpression, such as malignant mesothelioma and various solid tumors (5, 6). Pharmacological strategies primarily focus on small-molecule inhibitors that bind to the highly conserved palmitoylation pocket of TEAD proteins or disrupt the TEAD-YAP/TAZ protein-protein interaction (5, 12). While promising, therapeutic development faces challenges such as potential renal toxicity and the need for selectivity among TEAD paralogs to minimize off-target effects in normal tissues where Hippo signaling maintains homeostasis (6, 7).

Other names

Transcriptional enhancer factor TEF-5TEF-5DTEF-1TEAD-3TEA domain family member 3

Inhibition of the interaction between TEAD and its co-activators YAP/TAZ, often through competitive binding to the TEAD palmitoylation pocket or direct disruption of the protein-protein interaction interface.