TEA domain family member 1 (TEAD1) (TEAD1)

TEA domain family member 1 (TEAD1) is a member of the TEAD transcription factor family and serves as the primary nuclear effector of the Hippo signaling pathway (UniProt P28347). It functions by binding to transcriptional co-activators, such as Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-binding motif (TAZ), to drive the expression of genes involved in cell survival and proliferation (PMID: 34645841). In many cancers, particularly those with NF2 mutations or Hippo pathway inactivation, the TEAD1-YAP/TAZ complex is constitutively active, promoting tumor growth and therapeutic resistance (PMID: 35914444). While pan-TEAD inhibitors are being developed, there is a specific focus on paralog-selective inhibitors targeting TEAD1, such as IK-930, to potentially improve the therapeutic window and mitigate toxicities like renal dysfunction (Ikena Oncology, 2023). These inhibitors typically target the highly conserved palmitoylation pocket of TEAD1, which is essential for its structural stability and its ability to interact with YAP/TAZ (PMID: 35914444). Beyond oncology, mutations in TEAD1 are also linked to Sveinsson's chorioretinal atrophy, highlighting its importance in tissue-specific homeostasis (PMID: 30305530).

Other names

Transcriptional enhancer factor TEF-1Transcription factor 13TCF-13NTEF-1TEA domain family member 1

Small molecule inhibition of the TEAD1 palmitoylation pocket, which prevents the recruitment of YAP/TAZ co-activators and subsequent transcriptional activation of pro-proliferative genes (PMID: 35914444).