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| Status |
Public on Jan 14, 2021 |
| Title |
Activation of YAP-dependent Proliferation by a Small Molecule Targeting Annexin A2 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The transcriptional coactivator YAP orchestrates a pro-proliferative transcriptional program that controls the fate of somatic stem cells and the regenerative responses of certain tissues. As such, agents that activate YAP may hold therapeutic potential in disease states exacerbated by insufficient proliferative repair. Here we report the discovery of a small molecule, termed PY-60, which robustly activates YAP transcriptional activity in vitro and promotes YAP-dependent expansion of epidermal keratinocytes in mouse upon topical administration of drug. Chemical proteomics revealed the relevant target of PY-60 to be Annexin A2 (ANXA2), a protein that directly associates with YAP at the cell membrane in response to increased cell density. PY-60 treatment liberates ANXA2 from the membrane, ultimately promoting a phosphatase bound, non-phosphorylated, and transcriptionally active form of YAP. This work reveals ANXA2 to be a previously undescribed, druggable component of the Hippo pathway and suggests a mechanistic rationale for promoting YAP-dependent regenerative repair in disease.
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| |
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| Overall design |
Comparisons of the transcriptomes of 293A cells treated with DMSO vs PY-60
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| |
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| Contributor(s) |
Grzelak EM, Bollong MJ, Ibrahim LH |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jan 13, 2021 |
| Last update date |
Jan 15, 2021 |
| Contact name |
Lara Ibrahim |
| Organization name |
Scripps Research
|
| Street address |
10550 N Torrey Pines Rd
|
| City |
San Diego |
| State/province |
California |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
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| Platforms (1) |
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| Samples (6)
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| GSM5019784 |
DMSO treated control – Biological replicate 1 |
| GSM5019785 |
DMSO treated control – Biological replicate 2 |
| GSM5019786 |
DMSO treated control – Biological replicate 3 |
|
| Relations |
| BioProject |
PRJNA691981 |
| SRA |
SRP301664 |
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