ArticleOncogene2018
cAMP-independent non-pigmentary actions of variant melanocortin 1 receptor: AKT-mediated activation of protective responses to oxidative DNA damage.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Rationale of renewed efforts in developing MC4R modulators to treat metabolic disorders.Acta pharmaceutica Sinica. B · 2026Review
- PKA prevents the resection of DNA double-strand breaks and favours nonhomologous end-joining.Scientific reports · 2025Article
- Treatment of nitrogen mustard-induced corneal injury with alpha-melanocyte stimulating hormone.Experimental eye research · 2025Article
- FBXW7/GSK3β-mediated proline-rich 11 degradation promotes oxidative DNA damage and inhibits tumor progression in renal cell carcinoma.Theranostics · 2025Article
- An overview of benefits and risks of chronic melanocortin-1 receptor activation.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025Review
- Journey through the spectacular landscape of melanocortin 1 receptor.Pigment cell & melanoma research · 2024Review
- Review
- The biochemistry of melanogenesis: an insight into the function and mechanism of melanogenesis-related proteins.Frontiers in molecular biosciences · 2024Review
- A Side-by-Side Comparison of Wildtype and Variant Melanocortin 1 Receptor Signaling with Emphasis on Protection against Oxidative Damage to DNA.International journal of molecular sciences · 2023Article
- MC1R signaling through the cAMP-CREB/ATF-1 and ERK-NFκB pathways accelerates G1/S transition promoting breast cancer progression.NPJ precision oncology · 2023Article
- Alpha-melanocyte stimulating hormone (α-MSH): biology, clinical relevance and implication in melanoma.Journal of translational medicine · 2023Review
- Melanocortin 1 Receptor (MC1R): Pharmacological and Therapeutic Aspects.International journal of molecular sciences · 2023Review
- The αMSH-Dependent PI3K Pathway Supports Energy Metabolism, via Glucose Uptake, in Melanoma Cells.Cells · 2023Article
- Cutaneous Melanoma and Glioblastoma Multiforme Association-Case Presentation and Literature Review.Diagnostics (Basel, Switzerland) · 2023Article
- MGRN1 as a Phenotypic Determinant of Human Melanoma Cells and a Potential Biomarker.Life (Basel, Switzerland) · 2022Article
- Review
- Focus on the Contribution of Oxidative Stress in Skin Aging.Antioxidants (Basel, Switzerland) · 2022Review
- Review
- The Emerging Roles and Therapeutic Implications of Epigenetic Modifications in Ovarian Cancer.Frontiers in endocrinology · 2022Review
- Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The melanocortin 1 receptor gene (MC1R), a well-established melanoma susceptibility gene, regulates the amount and type of melanin pigments formed within epidermal melanocytes. MC1R variants associated with increased melanoma risk promote the production of photosensitizing pheomelanins as opposed to photoprotective eumelanins. Wild-type (WT) MC1R activates DNA repair and antioxidant defenses in a cAMP-dependent fashion. Since melanoma-associated MC1R variants are hypomorphic in cAMP signaling, these non-pigmentary actions are thought to be defective in MC1R-variant human melanoma cells and epidermal melanocytes, consistent with a higher mutation load in MC1R-variant melanomas. We compared induction of antioxidant enzymes and DNA damage responses in melanocytic cells of defined MC1R genotype. Increased expression of catalase (CAT) and superoxide dismutase (SOD) genes following MC1R activation was cAMP-dependent and required a WT MC1R genotype. Conversely, pretreatment of melanocytic cells with an MC1R agonist before an oxidative challenge with Luperox decreased (i) accumulation of 8-oxo-7,8-dihydro-2'-deoxyguanine, a major product of oxidative DNA damage, (ii) phosphorylation of histone H2AX, a marker of DNA double-strand breaks, and (iii) formation of DNA breaks. These responses were comparable in cells WT for MC1R or harboring hypomorphic MC1R variants without detectable cAMP signaling. In MC1R-variant melanocytic cells, the DNA-protective responses were mediated by AKT. Conversely, in MC1R-WT melanocytic cells, high cAMP production downstream of MC1R blocked AKT activation and was responsible for inducing DNA repair. Accordingly, MC1R activation could promote repair of oxidative DNA damage by a cAMP-dependent pathway downstream of WT receptor, or via AKT in cells of variant MC1R genotype.
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