# Targeting dynamic palmitoylation of TEAD transcription factors

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $547,945

## Abstract

Deregulation of Hippo–YAP signaling is implicated in diverse human cancers. TEAD
transcription factors bind to the transcription co-activators YAP/TAZ, and control the
transcriptional output of the Hippo pathway. However, it remains difficult to directly target
TEAD–YAP by small molecules. We previously discovered that TEADs possess intrinsic
“enzyme-like” activities and undergo autopalmitoylation (16-carbon fatty acylation).
Palmitoylation is critical for TEAD protein stability and transcriptional activation. We recently
discovered that ABHD1 is a novel depalmitoylase regulating TEADs. Loss of ABHD1 in cancers
might lead to sustained TEAD palmitoylation and activation of TEAD–YAP. In addition, we
identified MGH-CP1 as novel chemical inhibitor of TEAD palmitoylation, providing a
pharmacological tool to suppress TEAD–YAP activates in cancers.
Our specific aims of this proposal include: (1) to investigate the role of ABHD1 in regulation of
TEAD depalmitoylation; (2) To optimize MGH-CP1 and develop potent and selective TEAD
inhibitors. (3) To target TEAD–YAP transcriptional complex in vitro and in vivo using
pharmacological tools.

## Key facts

- **NIH application ID:** 9870917
- **Project number:** 5R01CA238270-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Junhao Mao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $547,945
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870917

## Citation

> US National Institutes of Health, RePORTER application 9870917, Targeting dynamic palmitoylation of TEAD transcription factors (5R01CA238270-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9870917. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*