TEA domain transcription factor 1 (TEAD1) (TEAD1)

The TEA domain transcription factor 1 (TEAD1) is a key member of the TEAD family of transcription factors, characterized by a conserved TEA DNA-binding domain that recognizes MCAT elements (5'-CATTCCA/T-3') and a C-terminal domain for cofactor binding, including YAP/TAZ from the Hippo pathway. TEAD1 cannot activate transcription alone and requires coactivators like YAP, TAZ, SRC family proteins, and VGLL proteins to regulate genes involved in heart, skeletal, and smooth muscle development, as well as cell proliferation, apoptosis, migration, and epithelial-mesenchymal transition. In the Hippo signaling pathway, TEAD1 mediates YAP/TAZ effects on organ size control and tumor suppression by restricting proliferation. Dysregulation of TEAD1 occurs in cancers such as Kaposi sarcoma (300-fold increase), basal-like breast cancer, ovarian cancer (promoting stemness and chemoresistance), glioblastoma, and liver cancer, where it drives pro-proliferative genes like c-myc, survivin, CTGF, Cyr61, and Axl. Mutations cause Sveinsson chorioretinal atrophy, highlighting its developmental role. As a therapeutic target, TEAD1 inhibition via small molecules like TM2 (blocks palmitoylation, IC50 38-156 nM) or verteporfin (disrupts YAP-TEAD) shows antiproliferative effects in YAP-dependent cancers, often enhanced with MEK inhibitors, though challenges include tissue-specific functions and potential impacts on differentiation.

Other names

Transcriptional enhancer factor TEF-1TEA domain family member 1Transcription factor 13 (TCF-13)NTEF-1Protein GT-IIC

Inhibition of TEAD palmitoylation, Disruption of YAP/TAZ-TEAD interaction, Suppression of TEAD-YAP transcriptional activity