TEA domain family transcription factor (TEAD)

TEA domain family transcription factors (TEADs) are a group of highly conserved nuclear proteins (TEAD1, TEAD2, TEAD3, and TEAD4 in mammals) that serve as the primary transcriptional effectors of the Hippo signaling pathway[5][7]. TEADs possess a DNA-binding TEA/ATTS domain and a C-terminal coactivator-binding domain. They require association with cofactors—most notably YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif)—to activate transcription of genes involved in cell proliferation, survival, and differentiation[1][2][3][5][7]. TEAD family members regulate critical processes in embryogenesis and organ development; they are also implicated in driving tumorigenesis through the expression of genes such as CTGF, CYR61, MYC, and GLI2[1][2][5][7]. Aberrant TEAD activity, frequently due to Hippo pathway inactivation, underlies many cancers and fibrotic diseases, making TEADs important emerging therapeutic targets[5][7]. Direct pharmacological modulation of TEAD is challenging due to their protein–protein interaction-dependent activity, but drug discovery efforts are ongoing[7].

Other names

TEAD family transcription factorTEA/ATTS domain transcription factorTranscriptional enhancer factor (TEF) familyTEAD1TEAD2TEAD3TEAD4

Inhibition of TEAD–YAP (or TEAD–TAZ) interaction (prevents transcriptional activation of proliferation-related genes)[7]. Modulation of transcription of genes downstream of the Hippo pathway[7]. Suppression of target gene expression via cofactor inhibition