TEA domain family member 4 (TEAD4) (TEAD4)

TEA domain family member 4 (TEAD4) is a member of the TEA/ATTS domain-containing family of transcription factors and serves as a primary nuclear effector of the Hippo signaling pathway (UniProt: Q15561). It plays a critical role in embryonic development, particularly in the specification of the trophectoderm, and in adult tissues, it regulates cell proliferation, apoptosis, and organ size (NCBI Gene: 7004). In the context of oncology, TEAD4 is frequently overexpressed or hyperactivated through its interaction with the co-activators YAP and TAZ, driving the expression of pro-growth and anti-apoptotic genes in various solid tumors, including mesothelioma and gastric cancer (PubMed: 30236343). Therapeutic strategies targeting TEAD4 focus on small-molecule inhibitors that bind to a conserved hydrophobic pocket, known as the palmitoylation pocket, to disrupt the formation of the TEAD-YAP/TAZ transcriptional complex (PubMed: 33571116). Several TEAD inhibitors, such as IK-930 and VT-107, are currently under clinical investigation for patients with YAP/TAZ-dependent cancers, particularly those harboring NF2 mutations (ClinicalTrials.gov: NCT05228015). These drugs aim to restore pathway control and inhibit tumor growth by preventing the transcription of oncogenic targets like CTGF and CYR61. While promising, targeting TEAD4 requires careful consideration of potential effects on normal tissue homeostasis, particularly in the kidneys where the Hippo pathway is active.

Other names

Transcription factor 13-like 1TEF-3RTEF-1TCF13L1hRTEF-1EFTR-2

Inhibition of the interaction between TEAD transcription factors and their co-activators YAP and TAZ, often by binding to the highly conserved palmitoylation pocket or through covalent modification of a conserved cysteine residue (PubMed: 33571116).