Target intelligence / Profile preview

TEA domain transcription factor 1, TEA domain transcription factor 3, and TEA domain transcription factor 4 (TEAD1, TEAD3, TEAD4)

Target
TEAD1, TEAD3, TEAD4
Molecular classification
Transcription factor, DNA-binding protein, Multigene family
01

Overview

The TEAD transcription factor family comprises highly conserved DNA-binding proteins (TEAD1, TEAD3, TEAD4) that regulate gene expression via interaction with coactivators—primarily YAP and TAZ—in the Hippo signaling pathway. They control cell proliferation, differentiation, and organ size during development. In adult tissues, TEAD activity sustains stem cell populations and influences regeneration. Aberrant TEAD activity, often driven by dysregulated Hippo pathway, contributes to oncogenesis by promoting EMT, cellular proliferation, and survival. TEAD proteins interact with other signaling inputs, including TGF-β and SMADs, impacting fibrosis and cancer progression. Targeting the TEAD-YAP/TAZ interface is an emerging strategy in drug discovery, although direct pharmacological inhibition remains challenging due to the transcriptional nature of the proteins.

Other names
Transcription enhancer factor TEF-1TEF1Transcription enhancer factor TEF-5TEF5Transcription enhancer factor TEF-3TEF3
02

Mechanism of action

Inhibitors disrupt the TEAD-YAP/TAZ interaction, preventing the transcription of pro-growth and survival genes.

03

Biological functions

Regulation of gene expressionStem cell potency and lineage specificationCell proliferationCell differentiationCardiac and muscle developmentOrgan size controlEpithelial-mesenchymal transition (EMT)
04

Disease associations

Cancer (including breast cancer, mesothelioma, and others)FibrosisDevelopmental disorders
05

Safety considerations

Challenges include targeting transcription factors directly due to their lack of enzymatic activityRisk of off-target effects impacting development and organ homeostasis
06

Interacting drugs

small molecule inhibitors (preclinical development) targeting TEAD-YAP/TAZ interaction
07

Biomarkers

YAP/TAZ nuclear localization (for Hippo pathway activity)CTGF (connective tissue growth factor)CYR61 (cysteine-rich angiogenic inducer 61)

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