ArticleCancer research2023
AMPK Phosphorylates ZDHHC13 to Increase MC1R Activity and Suppress Melanomagenesis.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- A ZDHHC3-USP5-PTRF axis links palmitoylation to ferroptosis-associated phenotypes in melanoma.Cell death & disease · 2026Article
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- The Roles of ProteinCancer communications (London, England) · 2026Review
- S-acyl transferase ZDHHC13 modulates tumor microenvironment interactions to suppress metastasis in melanoma models.The Journal of clinical investigation · 2025Article
- A novel palmitoylation-based molecular signature reveals COX6A1 as a key regulator in metabolic dysfunction-associated steatotic liver disease.Journal of translational medicine · 2025Article
- S-palmitoylation of c-MET by CK2α-mediated zDHHC15 phosphorylation drives glioblastoma stem cell tumorigenicity.Neuro-oncology · 2025Article
- Palmitic acid and palmitoylation in cancer: Understanding, insights, and challenges.Innovation (Cambridge (Mass.)) · 2025Review
- Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential.International journal of cardiology. Heart & vasculature · 2025Review
- zDHHC-Mediated S-Palmitoylation in Skin Health and Its Targeting as a Treatment Perspective.International journal of molecular sciences · 2025Review
- Palmitoylation-dependent regulation of GPX4 suppresses ferroptosis.Nature communications · 2025Article
- Article
- DNA Methylation-Regulated ZDHHC17 Promotes the Risk of Facial Skin Aging.Clinical, cosmetic and investigational dermatology · 2025Article
- Recapitulating the potential contribution of protein S-palmitoylation in cancer.Cancer metastasis reviews · 2024Review
- S-acylation of CaChronic diseases and translational medicine · 2024Review
- Inhibiting S-palmitoylation arrests metastasis by relocating Rap2b from plasma membrane in colorectal cancer.Cell death & disease · 2024Article
- Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy.Nature communications · 2024Article
- Multicenter proteome-wide Mendelian randomization study identifies causal plasma proteins in melanoma and non-melanoma skin cancers.Communications biology · 2024Article
- Smad7 palmitoylation by the S-acyltransferase zDHHC17 enhances its inhibitory effect on TGF-β/Smad signaling.The Journal of biological chemistry · 2024Article
- ZDHHC20-mediated S-palmitoylation of YTHDF3 stabilizes MYC mRNA to promote pancreatic cancer progression.Nature communications · 2024Article
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Inherited genetic variations in the melanocortin-1 receptor (MC1R) responsible for human red hair color (RHC) variants are associated with impaired DNA damage repair and increased melanoma risk. MC1R signaling is critically dependent on palmitoylation, primarily mediated by the protein acyltransferase zinc finger DHHC-type palmitoyltransferase 13 (ZDHHC13). A better understanding of how ZDHHC13 is physiologically activated could help identify approaches to prevent melanomagenesis in redheads. Here, we report that AMP-activated protein kinase (AMPK) phosphorylates ZDHHC13 at S208 to strengthen the interaction between ZDHHC13 and MC1R-RHC, leading to enhanced MC1R palmitoylation in redheads. Consequently, phosphorylation of ZDHHC13 by AMPK increased MC1R-RHC downstream signaling. AMPK activation and MC1R palmitoylation repressed UVB-induced transformation of human melanocytes in vitro and delayed melanomagenesis in vivo in C57BL/6J-MC1R-RHC mice. The importance of AMPK to MC1R signaling was validated in human melanomas where AMPK upregulation correlated with expression of factors downstream from MC1R signaling and with prolonged patient survival. These findings suggest AMPK activation as a promising strategy to reduce melanoma risk, especially for individuals with red hair. SIGNIFICANCE: Phosphorylation of ZDHHC13 by AMPK at S208 promotes MC1R activation and suppresses melanocyte transformation, indicating activation of AMPK as a potential approach to prevent melanoma in people with red hair.
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Registered trials
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