We sequenced 3201 bp upstream from the ATG translation start codon of the human melanocortin-1 receptor (MC1R). A number of transcriptional initiation sites were detected over a region of approximately 600 base pairs upstream of the receptor coding region. These consist of GC-rich regions, each including SP-1 consensus binding motifs. Neither a TATA nor a CAAT box was found in this region. The 5'-flanking region also contains the consensus regulatory elements for AP-1, AP-2, and several E-boxes. Gel shift assays targeting the three GC boxes confirmed binding of SP-1. A promoter assay revealed that the minimal region exhibiting promoter activity was located between nucleotides -517 and -282 in human melanoma SK-Mel-2 cells. Further deletion from -517 to -447, which removed an SP-1 site, completely abolished luciferase activity. In conclusion, the MC1R promoter shares the characteristics of many other GPCR promoters. These characteristics include GC-rich sequence, lack of a TATA box, and binding of SP-1.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1006/bbrc.1999.1228 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Discovery of MT-7117 (Dersimelagon Phosphoric Acid): A Novel, Potent, Selective, and Nonpeptidic Orally Available Melanocortin 1 Receptor Agonist.
J Med Chem
December 2024
Research Division, Mitsubishi Tanabe Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
Activation of the melanocortin 1 receptor (MC1R) mediates melanogenesis in melanocytes, anti-inflammatory effects in inflammatory cells, and antifibrotic effects in fibroblasts. Thus, MC1R agonists are expected to be beneficial for treating skin, autoimmune, inflammatory, and fibrotic diseases. Afamelanotide, an α-melanocyte-stimulating hormone (α-MSH) analogue MC1R agonist, is used clinically for treating erythropoietic protoporphyria (EPP) as a subcutaneous implant formulation.
View Article and Find Full Text PDFMelanocortin 1 receptor mediates melanin production by interacting with the BBSome in primary cilia.
PLoS Biol
December 2024
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, China.
Production of melanin pigments is a protective mechanism of the skin against ultraviolet (UV)-induced damage and carcinogenesis. However, the molecular basis for melanogenesis is still poorly understood. Herein, we demonstrate a critical interplay between the primary cilium and the melanocortin 1 receptor (MC1R) signaling.
View Article and Find Full Text PDFNovel Variants in Medium and Low Penetrance Predisposing Genes in a Hungarian Malignant Melanoma Cohort With Increased Risk.
Pigment Cell Melanoma Res
January 2025
Department of Medical Genetics, University of Szeged, Szeged, Hungary.
Both germline and somatic variants contribute to the genetic background and pathogenesis of melanoma. Germline variants include the presence of rare pathogenic or likely pathogenic variants of high, medium, and low penetrance melanoma-predisposing genes. Rare variants of high penetrance melanoma-predisposing genes are associated with melanoma development, whereas the medium and low penetrance predisposing genes can significantly increase melanoma risk.
View Article and Find Full Text PDFMn-labelled Beta-cyclodextrin for Melanoma Imaging: A Proof-of-concept Preclinical Study.
In Vivo
October 2024
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Background/aim: As prostaglandin E2 (PGE2) and its receptors (EP2) are over-expressed on tumor cells and microenvironment, radiolabeled cyclodextrins targeting such biomolecules are valuable vector candidates in molecular cancer diagnostics. Using experimental melanoma models, we evaluated the in vivo imaging behavior of novel Manganese-52-labeled (Mn) randomly methylated beta-cyclodextrin ([Mn]Mn-DOTAGA-RAMEB) and compared it with the following well-established tumor-specific probes: melanocortin-1 receptor (MC1-R)-affine [Ga]Ga-DOTA-NAPamide and PGE2 selective [Ga]Ga-DOTAGA-RAMEB cyclodextrin.
Materials And Methods: Post-injection of [Ga]Ga-DOTA-NAPamide, [Ga]Ga-DOTAGA-RAMEB, and [Mn]Mn-DOTAGA-RAMEB into MC1-R positive B16F10 melanoma-bearing mice, tumor radio-pharmaceutical uptake was quantified in vivo and ex vivo using preclinical positron emission tomography (PET) and high-performance gamma counter.
Ionic liquid combined with cationic liposome co-delivers microphthalmia-associated transcription factor small interfering RNA to regulate melanogenesis.
Int J Biol Macromol
November 2024
Sauvage Laboratory for Smart Materials, Harbin Institute of Technology, Shenzhen 518055, China. Electronic address:
Suppressing allele-specific genes using small interfering RNAs (siRNAs) can effectively whiten skin by influencing cellular gene and protein expression. Topical delivery of siRNA is a promising alternative to injections for RNA interference. However, the barrier function of the skin hinders the effective penetration of siRNA.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!