GO:0140552 TEAD-YAP complex: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0140552 (TEAD-YAP complex) is a transcription factor complex composed of one TEAD-family DNA-binding protein and the transcriptional coactivator YAP.
• The complex is the main nuclear effector of the Hippo signaling pathway and drives expression of genes controlling proliferation, survival, and migration.
• Genetic or pharmacological disruption of the TEAD-YAP complex suppresses YAP-driven oncogenic activity, validating it as a cancer target.
• The complex is regulated by upstream Hippo kinases, by MRTF-mediated potentiation, and by negative regulators such as RUNX3.
• Inhibition of YAP/TAZ-TEAD activity can drive differentiation programs, for example cytotrophoblast-to-syncytiotrophoblast transition.
• New heterobifunctional degraders that bind the TEAD lipid pocket can eliminate the TEAD-YAP/TAZ complex, expanding therapeutic options.
Description
The TEAD-YAP complex (GO:0140552) is a cellular-component ontology term describing a transcription factor complex that contains one DNA-binding protein of the TEAD family and the transcriptional coactivator YAP. This complex is the principal nuclear output of the Hippo signaling pathway and converts mechanical and biochemical cues into changes in gene expression that control cell proliferation, survival, and migration. Because the complex directly binds enhancer and promoter elements through TEAD, it is a central node for understanding how cells interpret growth signals. Researchers study GO:0140552 because its activity is frequently deregulated in human cancer and because it is experimentally tractable: genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP in model systems. The complex has also been implicated in non-malignant biology, including trophoblast differentiation, where inhibition of YAP/TAZ-TEAD activity induces cytotrophoblast differentiation into syncytiotrophoblast. Recent chemical-biology work has produced covalent disruptors of YAP-TEAD association and heterobifunctional degraders that bind the TEAD allosteric lipid pocket, showing that the complex can be selectively eliminated rather than simply inhibited. This makes GO:0140552 an attractive entry point for both mechanistic studies and therapeutic development.
TEAD-YAP complex At A Glance
| GO ID | GO:0140552 |
|---|---|
| GO term | TEAD-YAP complex |
| Ontology | cellular_component |
| Definition | A transcription factor complex that is composed of the one DNA binding protein of the TEAD family and the transcriptional coactivator YAP. |
| Synonyms | TEAD-1-YAP complex; TEAD-2 multiprotein complex; TEAD-2-YAP complex; TEAD-3-YAP complex; TEAD-4-YAP complex |
| Major function | Sequence-specific transcription factor complex that activates Hippo-pathway target genes controlling proliferation, survival, and migration. |
| Core subunits | One TEAD-family DNA-binding protein (TEAD1-TEAD4) plus the coactivator YAP. |
| Related coactivators | YAP paralog TAZ can substitute in related TEAD complexes, and MRTF can potentiate TEAD-YAP transcriptional activity. |
| Disease relevance | YAP-driven cancers; clear cell renal cell carcinoma; gastric cancer; trophoblast differentiation disorders. |
What Is GO:0140552?
According to the QuickGO definition, GO:0140552 (TEAD-YAP complex) is a transcription factor complex that is composed of one DNA binding protein of the TEAD family and the transcriptional coactivator YAP. In other words, it is a heteromeric nuclear complex in which a TEAD-family protein provides sequence-specific DNA binding and YAP provides the transcriptional activation function. The term is annotated as a cellular component and includes synonyms such as TEAD-1-YAP complex, TEAD-2 multiprotein complex, TEAD-2-YAP complex, TEAD-3-YAP complex, and TEAD-4-YAP complex, reflecting the four TEAD paralogs that can pair with YAP.
Why Is TEAD-YAP complex Important in Cell Biology?
GO:0140552 matters because it is the point at which Hippo signaling, mechanical cues, and oncogenic transcription converge. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP, establishing the complex itself, rather than YAP alone, as a therapeutic target. The complex also participates in context-dependent tumor-suppressive or differentiation-promoting programs, as shown by YAP-mediated repression of the TEAD-NF-kB complex in clear cell renal cell carcinoma and by YAP/TAZ-TEAD inhibition driving syncytiotrophoblast differentiation. Because the complex is a discrete molecular entity, it can be studied with precise CRISPR models and targeted degraders.
• Central nuclear effector of the Hippo pathway, linking upstream kinases to proliferative gene programs.
• Validated cancer dependency: disrupting the TEAD-YAP complex suppresses YAP-driven oncogenic activity.
• Context-dependent tumor suppressor roles, e.g. YAP represses the TEAD-NF-kB complex in clear cell renal cell carcinoma.
• Negative regulation by RUNX3 in gastric cancer highlights tissue-specific control of the complex.
• MRTF potentiates TEAD-YAP transcriptional activity and promotes metastasis.
• Inhibition of YAP/TAZ-TEAD activity induces cytotrophoblast differentiation into syncytiotrophoblast.
• Covalent disruptors of YAP-TEAD association provide chemical tools to probe the complex.
• Heterobifunctional degraders targeting the TEAD lipid pocket can eliminate the TEAD-YAP/TAZ complex.
• Provides a defined cellular-component target for CRISPR knockout, knock-in, and degron studies.
• Relevant to drug discovery, resistance mechanisms, and differentiation-based therapies.
Structure and Composition of TEAD-YAP complex
TEAD DNA-binding subunit
In simple terms: TEAD is the part of the complex that grabs onto DNA.
The TEAD subunit is one of four paralogs (TEAD1-TEAD4) and provides sequence-specific DNA binding for the complex. The QuickGO synonyms TEAD-1-YAP complex, TEAD-2-YAP complex, TEAD-3-YAP complex, and TEAD-4-YAP complex reflect that any of these TEAD proteins can form the DNA-binding half of GO:0140552. TEAD proteins also contain an allosteric lipid pocket that has been exploited by heterobifunctional small molecules to degrade the complex.
YAP coactivator subunit
In simple terms: YAP is the part that turns transcription on.
YAP is the transcriptional coactivator that partners with TEAD in GO:0140552. YAP does not bind DNA on its own; it is recruited to target enhancers through TEAD. Genetic and pharmacological disruption of the TEAD-YAP interaction suppresses the oncogenic activity of YAP, demonstrating that YAP function in this complex depends on TEAD association. Covalent disruptors of YAP-TEAD association further confirm that the physical YAP-TEAD interface is required for complex activity.
Assembly and stoichiometry
In simple terms: One TEAD and one YAP come together to form the active complex.
The QuickGO definition specifies a complex composed of one DNA-binding TEAD-family protein and the coactivator YAP, i.e. a heteromeric assembly rather than a large multi-subunit machine. Assembly is driven by protein-protein interaction between TEAD and YAP and is opposed by Hippo-pathway kinases that restrain YAP nuclear availability. The related coactivator TAZ can participate in TEAD complexes, and MRTF can potentiate TEAD-YAP transcriptional activity, indicating that complex composition and activity are modulated by additional factors.
Interaction with NF-kB and other transcription factors
In simple terms: The complex can also talk to other transcription factors.
In clear cell renal cell carcinoma, YAP represses the TEAD-NF-kB complex and inhibits tumor growth, showing that TEAD can engage NF-kB in a context-dependent manner. This illustrates that GO:0140552 does not act in isolation but can integrate with inflammatory signaling complexes at target genes.
Negative regulation by RUNX3
In simple terms: RUNX3 acts as a brake on the complex.
RUNX3 is a novel negative regulator of the oncogenic TEAD-YAP complex in gastric cancer, providing a tissue-specific mechanism that restrains complex activity. This finding supports the view that the complex is a discrete, regulatable entity whose abundance and activity can be modulated by partner proteins.
Key Genes Involved in GO:0140552 TEAD-YAP complex
The following genes and proteins are the principal components, regulators, and context-dependent partners of the TEAD-YAP complex (GO:0140552) as supported by the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| TEAD1 | DNA-binding subunit of the TEAD-YAP complex | Core component of GO:0140552; target for complex disruption |
| TEAD2 | DNA-binding subunit; synonym TEAD-2-YAP complex | Core component; allosteric lipid pocket for degraders |
| TEAD3 | DNA-binding subunit; synonym TEAD-3-YAP complex | Core component of the complex |
| TEAD4 | DNA-binding subunit; synonym TEAD-4-YAP complex | Core component of the complex |
| YAP1 | Transcriptional coactivator; oncogenic driver | Central to YAP-driven oncogenesis; disrupted by covalent inhibitors |
| WWTR1 (TAZ) | YAP paralog coactivator in TEAD complexes | Targeted by TEAD-YAP/TAZ degraders |
| RUNX3 | Negative regulator of oncogenic TEAD-YAP complex | Tumor suppressor context in gastric cancer |
| MRTF (MKL1/MKL2) | Potentiates TEAD-YAP transcriptional activity | Promotes metastasis via TEAD-YAP |
| NF-kB subunits | Form TEAD-NF-kB complexes repressed by YAP | Context-dependent tumor suppression in ccRCC |
| LATS1/2 kinases | Upstream Hippo kinases restraining YAP | Regulate complex assembly via YAP phosphorylation |
| STK3/STK4 (MST1/2) | Upstream Hippo kinases | Control Hippo signaling to the complex |
| VGLL4 | TEAD-binding cofactor competing with YAP | Modulates complex output |
| CTGF (CCN2) | Canonical YAP-TEAD target gene | Readout of complex activity |
| CYR61 (CCN1) | Canonical YAP-TEAD target gene | Readout of complex activity |
| AMOTL2 | Junction-associated Hippo regulator | Modulates YAP-TEAD activity |
| GATA3 | Trophoblast transcription factor cooperating with YAP/TAZ-TEAD | Differentiation studies in trophoblast |
| PPARG | Trophoblast differentiation regulator | Syncytiotrophoblast differentiation context |
How Is TEAD-YAP complex Regulated?
The TEAD-YAP complex is regulated at multiple levels. Upstream Hippo-pathway kinases control YAP nuclear availability, and disruption of the TEAD-YAP interaction suppresses YAP oncogenic activity, indicating that complex formation is a regulated step. MRTF potentiates TEAD-YAP transcriptional activity, adding a coactivator-level control mechanism that promotes metastasis. RUNX3 acts as a negative regulator of the oncogenic TEAD-YAP complex in gastric cancer, providing a tissue-specific brake. In clear cell renal cell carcinoma, YAP represses the TEAD-NF-kB complex, showing that the complex can be redirected toward different partner complexes depending on context. Finally, the TEAD allosteric lipid pocket can be engaged by heterobifunctional small molecules that degrade the TEAD-YAP/TAZ complex, demonstrating pharmacological control of complex abundance.
TEAD-YAP complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| YAP1 | YAP-driven cancers | TEAD-YAP complex knockout or point-mutation models |
| RUNX3 | Gastric cancer | RUNX3 knockout and TEAD-YAP reporter models |
| YAP1 / WWTR1 | Clear cell renal cell carcinoma | TEAD-NF-kB complex perturbation models |
| YAP1 / WWTR1 | Trophoblast differentiation | Human trophoblast differentiation models |
| MRTF (MKL1/MKL2) | Metastasis | MRTF overexpression and TEAD-YAP activity models |
YAP-driven cancers
Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP, establishing the complex as a cancer dependency in YAP-driven tumors. Covalent disruptors of YAP-TEAD association suppress defective Hippo signaling, providing chemical validation of the complex as a drug target. MRTF-mediated potentiation of TEAD-YAP transcriptional activity causes metastasis, linking complex hyperactivity to advanced disease.
Gastric cancer
RUNX3 is a novel negative regulator of the oncogenic TEAD-YAP complex in gastric cancer, suggesting that loss of this brake contributes to gastric tumorigenesis.
Clear cell renal cell carcinoma
In clear cell renal cell carcinoma, YAP represses the TEAD-NF-kB complex and inhibits tumor growth, revealing a context in which the TEAD-YAP axis is tumor-suppressive rather than oncogenic.
Trophoblast differentiation and placental biology
Inhibition of YAP/TAZ-TEAD activity induces cytotrophoblast differentiation into syncytiotrophoblast in human trophoblast, implicating the complex in placental development and differentiation disorders.
From TEAD-YAP complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is TEAD required for YAP-driven proliferation? | TEAD1-TEAD4 knockout cell models |
| Does disrupting the YAP-TEAD interface block oncogenic activity? | Point-mutation knock-in of the YAP-TEAD interface |
| Can the complex be degraded pharmacologically? | Tagged knock-in of TEAD for degrader studies |
| How does RUNX3 restrain the complex? | RUNX3 knockout and overexpression models |
| Does MRTF potentiate TEAD-YAP transcription? | MRTF overexpression models |
| Is YAP/TAZ-TEAD required for trophoblast differentiation? | YAP/TAZ-TEAD perturbation in trophoblast models |
How to Study the TEAD-YAP complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Expression of TEAD-YAP target genes | Readout of complex activity |
| Co-immunoprecipitation | Physical TEAD-YAP interaction | Complex detection and disruption |
| Proximity labeling | Near-neighbor interactions of TEAD or YAP | Complex composition studies |
| Degrader assays | Loss of TEAD-YAP/TAZ complex | Therapeutic validation |
| Proliferation assays | YAP-driven oncogenic growth | Cancer dependency studies |
| Migration assays | Metastatic potential | MRTF-TEAD-YAP studies |
| Differentiation assays | Syncytiotrophoblast formation | Trophoblast biology |
| Reporter assays | TEAD-dependent transcription | Complex activity quantification |
Transcriptomic readouts of complex activity
Because the TEAD-YAP complex is a transcription factor complex, RNA-seq of canonical target genes such as CTGF and CYR61 is a standard readout of its activity. Comparing knockout, point-mutant, and overexpressing lines allows researchers to separate TEAD-dependent from YAP-independent effects.
Protein interaction and complex detection
Co-immunoprecipitation and proximity-based assays can detect the TEAD-YAP interaction and its disruption by covalent inhibitors or degraders. Tagged knock-in of TEAD or YAP enables quantitative assessment of complex abundance after degrader treatment.
Chemical biology and degrader assays
Covalent disruptors of YAP-TEAD association and heterobifunctional degraders that bind the TEAD allosteric lipid pocket are used to probe complex function and to validate the complex as a therapeutic target.
Disease-relevant phenotypic assays
Proliferation, migration, and differentiation assays in cancer and trophoblast models link complex activity to phenotypes such as oncogenic growth, metastasis, and syncytiotrophoblast differentiation.
How CRISPR Can Be Used to Study GO:0140552 TEAD-YAP complex
Knockout
CRISPR knockout of TEAD paralogs or YAP1 is used to test whether the TEAD-YAP complex is required for proliferation and target-gene expression, as demonstrated by genetic disruption studies. Knockout of negative regulators such as RUNX3 can be used to model complex hyperactivation in gastric cancer.
Point Mutation
Point-mutation knock-in at the YAP-TEAD interface can be used to test whether the physical interaction is required for oncogenic activity, complementing covalent disruptor studies.
Knock-in
Tagged knock-in of TEAD or YAP enables detection of the endogenous complex and quantitative assessment of degrader-mediated elimination of the TEAD-YAP/TAZ complex.
Overexpression
Overexpression of YAP, TAZ, or MRTF is used to drive complex activity and model metastasis, as shown by MRTF potentiation of TEAD-YAP transcriptional activity. Overexpression models also help test whether complex inhibition reverses oncogenic phenotypes.
How EDITGENE Supports TEAD-YAP complex Research
Researchers studying TEAD-YAP complex-related genes often need to determine whether a candidate gene is causally involved in complex assembly, activity, or disease phenotypes. EDITGENE provides the CRISPR cell models and screening services needed to move from correlation to causation.
Contact EDITGENE today to design your custom CRISPR model for TEAD-YAP complex research.
Frequently Asked Questions About TEAD-YAP complex
What is the TEAD-YAP complex?
The TEAD-YAP complex (GO:0140552) is a transcription factor complex composed of one DNA-binding TEAD-family protein and the transcriptional coactivator YAP.
What genes are involved in the TEAD-YAP complex?
The core genes are TEAD1, TEAD2, TEAD3, TEAD4, and YAP1, with WWTR1 (TAZ) as a related coactivator and regulators such as RUNX3 and MRTF.
What is the function of GO:0140552?
It is the nuclear effector of Hippo signaling that activates genes controlling proliferation, survival, and migration.
Why is the TEAD-YAP complex important in cancer?
Disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP, making it a validated cancer target.
How is the TEAD-YAP complex regulated?
It is regulated by Hippo kinases, by MRTF potentiation, and by negative regulators such as RUNX3.
Can the TEAD-YAP complex be degraded?
Yes, heterobifunctional small molecules that bind the TEAD allosteric lipid pocket can degrade the TEAD-YAP/TAZ complex.
What diseases are linked to the TEAD-YAP complex?
YAP-driven cancers, gastric cancer, clear cell renal cell carcinoma, and trophoblast differentiation disorders.
What methods are used to study the TEAD-YAP complex?
RNA-seq, co-immunoprecipitation, proximity labeling, degrader assays, and phenotypic assays.
How do CRISPR models help study GO:0140552?
Knockout, point-mutation, knock-in, and overexpression models test whether TEAD and YAP are causally required for complex activity and disease phenotypes.
Is the TEAD-YAP complex always oncogenic?
No; in clear cell renal cell carcinoma, YAP represses the TEAD-NF-kB complex and inhibits tumor growth, showing context-dependent roles.
Conclusion
GO:0140552 (TEAD-YAP complex) is a discrete transcription factor complex that integrates Hippo signaling with proliferative and differentiation gene programs. Its central role in YAP-driven cancer, its context-dependent tumor suppressor functions, and its emerging druggability through covalent disruptors and degraders make it a high-value research target. Precise CRISPR models, including knockout, point-mutation, knock-in, and overexpression lines, are essential for establishing causality between the TEAD-YAP complex and disease phenotypes. EDITGENE provides these models and the associated screening and bioinformatics services to accelerate discovery.
References
- 1. Liu-Chittenden Y et al.. 2012. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP.. Genes Dev 26(12):1300-5 PMID: 22677547
- 2. Li Z et al.. 2024. YAP represses the TEAD-NF-κB complex and inhibits the growth of clear cell renal cell carcinoma.. Sci Signal 17(843):eadk0231 PMID: 38954637
- 3. Fan M et al.. 2022. Covalent disruptor of YAP-TEAD association suppresses defective Hippo signaling.. Elife 11 PMID: 36300789
- 4. Mizutani T et al.. 2022. Inhibition of YAP/TAZ-TEAD activity induces cytotrophoblast differentiation into syncytiotrophoblast in human trophoblast.. Mol Hum Reprod 28(10) PMID: 35993908
- 5. Qiao Y et al.. 2016. RUNX3 is a novel negative regulator of oncogenic TEAD-YAP complex in gastric cancer.. Oncogene 35(20):2664-74 PMID: 26364597
- 6. Kim T et al.. 2017. MRTF potentiates TEAD-YAP transcriptional activity causing metastasis.. EMBO J 36(4):520-535 PMID: 28028053
- 7. Yeh IJ et al.. 2026. Degradation of the TEAD•YAP/TAZ Transcription Factor Complex by Heterobifunctional Small Molecules that Bind to the TEAD Allosteric Lipid Pocket.. bioRxiv PMID: 41542630
- 8. Yeh IJ et al.. 2026. Degradation of the TEAD·YAP/TAZ Transcription Factor Complex by Heterobifunctional Small Molecules That Bind to the TEAD Allosteric Lipid Pocket.. ACS Chem Biol 21(5):1199-1210 PMID: 41949975
