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Updated: Jun 23, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Smad7 palmitoylation by the S-acyltransferase zDHHC17 enhances its inhibitory effect on TGF-β/Smad signaling

Oleksandr Voytyuk1, Yae Ohata1, Aristidis Moustakas1

  • 1Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Box 582, Biomedical Center, Uppsala University, Uppsala, Sweden.

The Journal of Biological Chemistry
|June 14, 2024
PubMed

Insights

Transforming growth factor-β (TGF-β) signaling is regulated by Smad7. This study reveals Smad7 undergoes S-palmitoylation, a modification enhancing its inhibitory role in TGF-β/Smad pathways.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Cancer research

Background:

  • Transforming growth factor-β (TGF-β) is a crucial cytokine regulating cell growth, differentiation, and development.
  • Smad7 acts as a negative feedback regulator of TGF-β signaling.
  • Post-translational modifications critically control Smad7 activity.

Purpose of the Study:

  • To investigate novel post-translational modifications of Smad7.
  • To elucidate the role of S-palmitoylation in Smad7 function.
  • To understand the impact of Smad7 S-palmitoylation on TGF-β signaling in mammary epithelial cells.

Main Methods:

  • Resin-assisted capture assays
  • Metabolic labeling techniques
  • Mammary epithelial cell models
  • Identification of palmitoylation sites using mass spectrometry (implied)

Main Results:

  • Smad7 is S-palmitoylated in mammary epithelial cells.
  • zDHHC17 mediates Smad7 S-palmitoylation.
  • Cysteine residues Cys415 and Cys417 are identified as key palmitoylation sites.
  • S-palmitoylation promotes Smad7 nuclear-to-cytoplasmic translocation and enhances protein stability.
  • Palmitoylated Smad7 more effectively inhibits TGF-β-induced Smad transcriptional responses.

Conclusions:

  • S-palmitoylation is a novel post-translational modification of Smad7.
  • This modification enhances Smad7's inhibitory capacity on TGF-β/Smad signaling.
  • Findings highlight the importance of S-palmitoylation in regulating TGF-β signaling, with implications for mammary development and cancer progression.
Keywords:
Smad7TGF-βpalmitoylationpost-translational modificationsignaling

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