TEA domain transcription factor (TEAD (family: TEAD1, TEAD2, TEAD3, TEAD4))

TEA domain transcription factors (TEADs) are a highly conserved family of DNA-binding proteins that function as transcription factors, characterized by a TEA domain responsible for sequence-specific DNA binding (to “MCAT” elements 5’-CATTCCA/T-3’)[1][3][5]. Humans possess four TEAD proteins (TEAD1–4), each with an N-terminal TEA/ATTS DNA binding domain and a C-terminal coactivator-binding domain[2][9]. TEADs are not transcriptionally active alone but require coactivators—primarily YAP and TAZ (core Hippo pathway effectors)—to activate gene expression governing cell proliferation, survival, differentiation, and organ development[2][9]. Their dysregulated activity, particularly via the YAP/TAZ-TEAD complex, is implicated in driving cancer proliferation, survival, and immune evasion, making them key targets for oncology drug discovery[6][9]. Approaches to inhibit TEADs focus on disrupting their interaction with coactivators or inhibiting their palmitoylation; several small-molecule inhibitors are in preclinical development[6]. TEAD factors are also involved in cardiac, skeletal, and smooth muscle development, and are evolutionarily conserved across metazoans and fungi[3][4][5][7].

Other names

Transcriptional enhancer factor (TEF)Transcription factor 13 (TCF-13) (specifically for TEAD1)Scalloped (Drosophila)TEC-1 (yeast)ABAA (fungal)

Inhibition of TEAD-YAP/TAZ interaction (blocks transcriptional activation of growth-promoting genes); Targeting palmitoylation site to disrupt TEAD protein stability or function