Transcriptional enhanced associate domain transcription factor 2 (TEAD2)

Transcriptional enhanced associate domain transcription factor 2 (TEAD2) is a key member of the TEA domain family of transcription factors and a primary nuclear effector of the Hippo signaling pathway [1][2]. It functions by forming complexes with the transcriptional co-activators YAP (Yes-associated protein) and TAZ (Transcriptional co-activator with PDZ-binding motif) to drive the expression of genes essential for cell proliferation, survival, and the epithelial-mesenchymal transition (EMT) [3]. In many human malignancies, such as malignant mesothelioma and hepatocellular carcinoma, the Hippo pathway is inactivated, leading to the hyperactivation of TEAD2 and subsequent tumor progression and metastasis [3][4]. Due to its central role in oncogenic signaling, TEAD2 is a high-priority therapeutic target in oncology. Current drug discovery efforts focus on small-molecule inhibitors that target the highly conserved palmitoylation pocket of TEAD proteins, which is necessary for their stability and interaction with YAP/TAZ [5]. While most clinical-stage candidates are pan-TEAD inhibitors targeting isoforms 1 through 4, TEAD2 specifically has been implicated in promoting resistance to conventional therapies and driving metastatic potential [4][6]. Clinical challenges include managing potential toxicities in tissues where Hippo signaling is required for homeostasis, such as the kidneys and intestinal epithelium [5]. Sources: [1] UniProt (Q15562) [2] NCBI Gene (7004) [3] PubMed (PMID: 33452133) [4] PubMed (PMID: 29330292) [5] Nature Reviews Drug Discovery (PMID: 35115533) [6] Cancer Research (PMID: 30133473)

Other names

TEA domain family member 2Transcription factor 13TEF-4ETFTcf-13

Inhibition of the protein-protein interaction between TEAD transcription factors and their co-activators YAP and TAZ, often by binding to the conserved hydrophobic palmitoylation pocket of the TEAD protein.