Molecular regulation of melanocyte senescence.

Cell senescence is the loss of ability to divide after a finite number of divisions, seen in normal mammalian somatic cells and often disrupted in cancer cells. The three genes so far associated with familial melanoma susceptibility--INK4A, CDK4 and ARF, are all implicated in the molecular pathways controlling cell senescence. Here we review those pathways, both as generally studied in fibroblasts and epithelial cells, and as specifically analysed in melanocytes. Key molecular effectors in melanocyte senescence appear to include some in common with other cell types - telomere attrition and the p16/RB pathway, and one that is not commonly mentioned in this connection, the cAMP signalling pathway that also regulates melanocyte differentiation. These findings are discussed in relation to the role of cell senescence in the development and molecular genetics of melanoma and its precursor lesions.