TEA domain family member 2 (TEAD2)

TEA domain family member 2 (TEAD2) is a transcription factor that serves as a primary downstream effector of the Hippo signaling pathway [1, 10]. It functions by binding to specific DNA sequences, such as M-CAT motifs, and recruiting transcriptional co-activators like YAP and TAZ to regulate genes essential for cell proliferation, survival, and organ size control [2, 8]. While TEAD2 is predominantly expressed during embryonic development—playing a critical role in neural tube closure—it is largely absent in most adult tissues but becomes aberrantly overexpressed in various malignancies, including hepatocellular carcinoma and gastric cancer [4, 7, 12]. In these disease contexts, TEAD2 promotes tumor progression, epithelial-mesenchymal transition (EMT), and resistance to therapies like sorafenib [5, 14, 15]. Therapeutic targeting of TEAD2 focuses on small-molecule inhibitors that either disrupt the TEAD-YAP/TAZ interaction or bind to a conserved hydrophobic pocket to inhibit TEAD palmitoylation, a post-translational modification required for its stability and activity [3, 10, 11].

Other names

ETFTEAD-2TEF-4TEF4TEA domain transcription factor 2

Inhibition of TEAD-YAP/TAZ protein-protein interaction or inhibition of TEAD palmitoylation by binding to the central hydrophobic pocket.