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Updated: Jan 25, 2026

A Fluorescence Fluctuation Spectroscopy Assay of Protein-Protein Interactions at Cell-Cell Contacts
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Cell contact and Nf2/Merlin-dependent regulation of TEAD palmitoylation and activity

Nam-Gyun Kim1,2, Barry M Gumbiner3,2,4

  • 1Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101.

Proceedings of the National Academy of Sciences of the United States of America
|May 3, 2019
PubMed

Insights

Cell density regulates TEAD protein activity and stability through palmitoylation, independent of the Hippo pathway kinase Lats. This involves fatty acid synthesis, depalmitoylation enzymes, and E3 ubiquitin ligase CHIP.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The Hippo pathway regulates organ size and cell proliferation through the YAP/TAZ transcriptional co-activators.
  • YAP/TAZ interact with TEAD transcription factors to control target gene expression.
  • TEAD protein activity and stability are crucial for cellular processes.

Purpose of the Study:

  • To investigate the regulation of TEAD protein activity and stability by cell density.
  • To determine the role of palmitoylation in TEAD regulation.
  • To elucidate the molecular mechanisms controlling TEAD function in response to cell contact.

Main Methods:

  • Analysis of TEAD palmitoylation and stability under varying cell densities.
  • Investigating the expression of enzymes involved in palmitate biosynthesis (FASN, ACC).
  • Assessing the impact of depalmitoylases (APT2, ABHD17A) and E3 ubiquitin ligase (CHIP) on TEAD.

Main Results:

  • TEAD palmitoylation is regulated by cell density, independent of Lats kinase.
  • Cell density reduces fatty acid synthase and acetyl-CoA carboxylase expression via Nf2/Merlin.
  • Palmitoylation-deficient TEAD mutants are unstable and degraded by the proteasome via CHIP.

Conclusions:

  • TEAD activity and stability are tightly controlled by cell density-dependent palmitoylation.
  • The regulation involves a coordinated interplay of fatty acid biosynthesis, depalmitoylation, and ubiquitination.
  • This mechanism provides a novel layer of control for TEAD function in response to cell contact.
Keywords:
Hippo signalingTEADdepalmitoylasefatty acid synthasepalmitoylation

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