ArticleProceedings of the National Academy of Sciences of the United States of America2024
Stearoylation cycle regulates the cell surface distribution of the PCP protein Vangl2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Deubiquitination of Vangl by USP6 and USP32 Regulates Planar Cell Polarity Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolites beyond metabolism: Exploring their atypical roles in protein modification and signaling transduction.Chinese medical journal · 2026Review
- LncRNA DNAJC3-AS1 promotes gastric cancer malignancy through miR-576-5p-mediated upregulation of LYPLA1.American journal of cancer research · 2026Article
- FGF receptor modulates planar cell polarity in the neuroectoderm via Vangl2 tyrosine phosphorylation.Nature communications · 2025Article
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
- Systematic analysis of ZDHHC9 as a potential prognostic and immunotherapy biomarker in breast cancer.Frontiers in immunology · 2025Article
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Authors and funding
5 authors.
Funding
Abstract
Defects in planar cell polarity (PCP) have been implicated in diverse human pathologies. Vangl2 is one of the core PCP components crucial for PCP signaling. Dysregulation of Vangl2 has been associated with severe neural tube defects and cancers. However, how Vangl2 protein is regulated at the posttranslational level has not been well understood. Using chemical reporters of fatty acylation and biochemical validation, here we present that Vangl2 subcellular localization is regulated by a reversible S-stearoylation cycle. The dynamic process is mainly regulated by acyltransferase ZDHHC9 and deacylase acyl-protein thioesterase 1 (APT1). The stearoylation-deficient mutant of Vangl2 shows decreased plasma membrane localization, resulting in disruption of PCP establishment during cell migration. Genetically or pharmacologically inhibiting ZDHHC9 phenocopies the effects of the stearoylation loss of Vangl2. In addition, loss of Vangl2 stearoylation enhances the activation of oncogenic Yes-associated protein 1 (YAP), serine-threonine kinase AKT, and extracellular signal-regulated protein kinase (ERK) signaling and promotes breast cancer cell growth and HRas G12V mutant (HRas
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