Transcriptional enhanced associate domain transcription factor 1 (TEAD1)

Transcriptional enhanced associate domain transcription factor 1 (TEAD1) is a key DNA-binding component of the Hippo signaling pathway, essential for regulating organ size, cell proliferation, and apoptosis (UniProt: P28347). TEAD1 lacks intrinsic transcriptional activity and must recruit co-activators, primarily Yes-associated protein (YAP) or Transcriptional co-activator with PDZ-binding motif (TAZ), to drive the expression of genes involved in tumor growth and survival (PubMed: 30447558). In various malignancies, such as malignant mesothelioma and hepatocellular carcinoma, the Hippo pathway is often inactivated—frequently via NF2 loss—leading to hyperactivation of TEAD1-mediated transcription (PubMed: 34644258). Therapeutic targeting of TEAD1 has emerged as a promising strategy, focusing on small molecules that either disrupt the TEAD-YAP/TAZ interaction or inhibit the auto-palmitoylation of TEAD1, a post-translational modification necessary for its structural stability and binding affinity (PubMed: 33005069). Clinical-stage inhibitors like IK-930 and VT-104 are currently being evaluated in patients with NF2-deficient solid tumors (ClinicalTrials.gov: NCT05228015). Beyond oncology, mutations in TEAD1 are associated with Sveinsson's chorioretinal atrophy, highlighting its critical role in ocular development and maintenance (PubMed: 18364390).

Other names

TEA domain family member 1Transcription factor 13TCF-13TEF-1NTEProtein scalloped-like

Inhibition of TEAD auto-palmitoylation or disruption of the TEAD-YAP/TAZ protein-protein interaction to prevent the transcriptional activation of oncogenic target genes.