ArticleThe Journal of biological chemistry2009
Mahogunin ring finger-1 (MGRN1) E3 ubiquitin ligase inhibits signaling from melanocortin receptor by competition with Galphas.
Article in The Journal of biological chemistry, 2009. 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, 52 citations in OpenAlex.
- MGRN1 in development and disease: a unifying view of a versatile membrane-tethered E3 ubiquitin ligase.Biochemical Society transactions · 2026Review
- The role of accessory proteins and co-factors in regulation of melanocortin-4 receptor signalling: An update.Journal of neuroendocrinology · 2026Review
- The E3 ubiquitin ligase MGRN1 targets melanocortin receptors MC1R and MC4R via interactions with transmembrane adapters.Journal of cell science · 2025Article
- AnInternational journal of molecular sciences · 2025Article
- Melanocortin-4 Receptor Antagonism Inhibits Colorectal and Anaplastic Thyroid Cancer In Vitro and In Vivo.Journal of clinical medicine · 2025Article
- MGRN1 as a Phenotypic Determinant of Human Melanoma Cells and a Potential Biomarker.Life (Basel, Switzerland) · 2022Article
- Concurrent outcomes from multiple approaches of epistasis analysis for human body mass index associated loci provide insights into obesity biology.Scientific reports · 2022Article
- Mahogunin Ring Finger 1 regulates pigmentation by controlling the pH of melanosomes in melanocytes and melanoma cells.Cellular and molecular life sciences : CMLS · 2021Article
- Review
- A genome-wide scan study identifies a single nucleotide substitution in MC1R gene associated with white coat colour in fallow deer (Dama dama).BMC genetics · 2020Article
- Mahogunin Ring Finger 1 Is Required for Genomic Stability and Modulates the Malignant Phenotype of Melanoma Cells.Cancers · 2020Article
- Elucidation of Melanogenesis Cascade for Identifying Pathophysiology and Therapeutic Approach of Pigmentary Disorders and Melanoma.International journal of molecular sciences · 2020Review
- The melanocortin pathway and control of appetite-progress and therapeutic implications.The Journal of endocrinology · 2019Review
- Conjugation with Dihydrolipoic Acid Imparts Caffeic Acid Ester Potent Inhibitory Effect on Dopa Oxidase Activity of Human Tyrosinase.International journal of molecular sciences · 2018Article
- Expression and Distribution of the Guanine Nucleotide-binding Protein Subunit Alpha-s in Mice Skin Tissues and Its Association with White and Black Coat Colors.Asian-Australasian journal of animal sciences · 2016Article
- Mahogunin Ring Finger-1 (MGRN1), a Multifaceted Ubiquitin Ligase: Recent Unraveling of Neurobiological Mechanisms.Molecular neurobiology · 2016Review
- Intracellular signaling mechanisms of the melanocortin receptors: current state of the art.Cellular and molecular life sciences : CMLS · 2015Review
- Suppressor mutations in the Glutamine Dumper1 protein dissociate disturbance in amino acid transport from other characteristics of the Gdu1D phenotype.Frontiers in plant science · 2015Article
- Functional conservation between mammalian MGRN1 and plant LOG2 ubiquitin ligases.FEBS letters · 2013Article
- Malignant melanoma and melanocortin 1 receptor.Biochemistry. Biokhimiia · 2013Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mahogunin ring finger-1 (MGRN1) is a RING domain-containing ubiquitin ligase mutated in mahoganoid, a mouse mutation causing coat color darkening, congenital heart defects, high embryonic lethality, and spongiform neurodegeneration. The melanocortin hormones regulate pigmentation, cortisol production, food intake, and body weight by signaling through five G protein-coupled receptors positively coupled to the cAMP pathway (MC1R-MC5R). Genetic analysis has shown that mouse Mgrn1 is an accessory protein for melanocortin signaling that may inhibit MC1R and MC4R by unknown mechanisms. These melanocortin receptors (MCRs) regulate pigmentation and body weight, respectively. We show that human melanoma cells express 4 MGRN1 isoforms differing in the C-terminal exon 17 and in usage of exon 12. This exon contains nuclear localization signals. MGRN1 isoforms decreased MC1R and MC4R signaling to cAMP, without effect on beta(2)-adrenergic receptor. Inhibition was independent on receptor plasma membrane expression, ubiquitylation, internalization, or stability and occurred upstream of Galpha(s) binding to/activation of adenylyl cyclase. MGRN1 co-immunoprecipitated with MCRs, suggesting a physical interaction of the proteins. Significantly, overexpression of Galpha(s) abolished the inhibitory effect of MGRN1 and decreased co-immunoprecipitation with MCRs, suggesting competition between MGRN1 and Galpha(s) for binding to MCRs. Although all MGRN1s were located in the cytosol in the absence of MCRs, exon 12-containing isoforms accumulated in the nuclei upon co-expression with the receptors. Therefore, MGRN1 inhibits MCR signaling by a new mechanism involving displacement of Galpha(s), thus accounting for key features of the mahoganoid phenotype. Moreover, MGRN1 might provide a novel pathway for melanocortin signaling from the cell surface to the nucleus.
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