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Updated: Aug 12, 2025

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
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Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model

Published on: September 7, 2013

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AMPK Phosphorylates ZDHHC13 to Increase MC1R Activity and Suppress Melanomagenesis

Yu Sun1, Xin Li2, Chengqian Yin2

  • 1Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.

Cancer Research
|January 26, 2023
PubMed

Insights

AMP-activated protein kinase (AMPK) activates zinc finger DHHC-type palmitoyltransferase 13 (ZDHHC13), enhancing melanocortin-1 receptor (MC1R) signaling. This pathway may prevent melanoma, particularly in redheads with higher MC1R risk.

Area of Science:

  • Molecular biology
  • Cancer research
  • Genetics

Background:

  • Genetic variations in MC1R cause red hair and increase melanoma risk due to impaired DNA repair.
  • MC1R signaling relies on palmitoylation by ZDHHC13, but its activation is not fully understood.

Purpose of the Study:

  • To investigate the physiological activation of ZDHHC13.
  • To identify strategies for preventing melanoma in individuals with red hair.

Main Methods:

  • Investigated the role of AMPK in ZDHHC13-MC1R interaction and palmitoylation.
  • Assessed the effects of AMPK activation on melanocyte transformation and melanoma development in vitro and in vivo.
  • Correlated AMPK levels with MC1R signaling and patient survival in human melanomas.

Main Results:

  • AMPK phosphorylates ZDHHC13 at S208, enhancing ZDHHC13-MC1R interaction and MC1R palmitoylation.
  • AMPK activation and MC1R palmitoylation inhibited UVB-induced melanocyte transformation and delayed melanoma in mice.
  • Increased AMPK levels in human melanomas correlated with downstream MC1R signaling and better patient survival.

Conclusions:

  • AMPK activation of ZDHHC13 enhances MC1R signaling and suppresses melanoma development.
  • AMPK activation represents a potential therapeutic strategy to reduce melanoma risk, especially in redheads.

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