What is the MC1R pathway?
The melanocortin 1 receptor (MC1R) is a G protein-coupled receptor crucial for the regulation of melanocyte proliferation and function. Upon binding melanocortins, MC1R activates several signaling cascades, notably the cAMP pathway leading to synthesis of photoprotective eumelanin.
What does the MC1R receptor do?
The MC1R gene provides instructions for making a protein called the melanocortin 1 receptor. This receptor plays an important role in normal pigmentation. The receptor is primarily located on the surface of melanocytes, which are specialized cells that produce a pigment called melanin.
What activates MC1R?
The MC1R protein lies within the cell membrane, and is signalled by melanocyte-stimulating hormone (MSH) released by the pituitary gland. When activated by one of the variants of MSH, typically α-MSH, MC1R initiates a complex signaling cascade that leads to the production of the brown or black pigment eumelanin.
Where is MC1R expressed?
MC1R is a receptor expressed in melanocytes that is activated by melanocortins such as α-MSH. Upon being stimulated, MC1R increases the levels of intracellular cAMP, which induces melanogenesis. In addition to constitutive pigmentation, facultative pigmentation induced by UV exposure is also controlled by MC1R.
What regulates MC1R?
The melanocortin 1 receptor (MC1R) is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk.
How does MC1R cause melanoma?
For example, MC1R controls ultraviolet B (UVB)-induced G1-like cell cycle arrest and subsequent onset of premature senescence in melanocytes, abrogation of which contributes to melanoma development14. Moreover, MC1R signaling plays an important role in promoting efficient DNA-damage repair10,15,16,17,18,19,20.
What is familial melanoma?
Familial malignant melanoma is a term usually referring to families in which 2 or more first-degree relatives, such as a parent, sibling, and/or child, have a type of skin cancer called melanoma. Cancer begins when healthy cells begin to change and grow, out of control forming a mass called a tumor.
Is MC1R an allele?
Human MC1R sequence variants are associated with red hair and fair skin in the Caucasian population (16–19). These variant alleles are extremely common; in northern European populations <50% of the MC1R genes encode the ‘wild-type’ or consensus protein.
How long is the MC1R gene?
The 315 amino acid murine homolog, Mc1r, was also cloned and identified Mountjoy et al. (1992) and mapped to the extension locus Robbins et al. (1993).
What type of mutation is MC1R?
Loss-of-function mutations at the MC1R are associated with a switch from eumelanin to phaeomelanin production, resulting in a red or yellow coat colour. Activating mutations, in animals at least, lead to enhanced eumelanin synthesis. In man, a number of loss-of-function mutations in the MC1R have been described.
How many base pairs is MC1R?
150 base pairs
transcriptional regulation of the melanocyte-specific MC1R gene requires an internal promoter located in the 150 base pairs upstream the initiation codon. MC1R variant is associated with multiple primary melanoma.
Is MC1R dominant or recessive?
We have investigated 174 individuals from 11 large kindreds with a preponderance of red hair and an additional 99 unrelated redheads, for MC1R variants and have confirmed that red hair is usually inherited as a recessive characteristic with the R151C, R160W, D294H, R142H, 86insA and 537insC alleles at this locus.
What are the signaling pathways and processes in pancreatic cancer?
Core signaling pathways and processes genetically altered in most pancreatic cancers. A complete listing of the gene sets defining these signaling pathways and processes and the statistical significance of each gene set are provided in table S8. Regulatory process or pathway Number of genetically altered genes detected
What is the structure of the MC1R gene?
Compared with most GPCR genes, the structure of MC1R is quite complex, as it displays several splice variants and a high degree of polymorphism. MC1R was first reported as intronless, but further analysis established that it actually comprises 4 exons and yields several transcripts as a result of intra- and intergenic splicing.
Does the hmgb1/rage inflammatory pathway promote pancreatic tumor growth?
The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics. Oncogene. 2014;33:567–577. doi: 10.1038/onc.2012.631.
Is MC1R only in melanocytes?
MC1R expression is not restricted to melanocytes and has been observed in other cell types including keratinocytes, fibroblasts, monocytes, dendritic cells and endothelial cells [90], [91], [92]. Of note, it has been shown that activation of MC1R by αMSH leads to cAMP- and PKA-dependent inhibition of p38 in leukocytes [93].