University of Iceland
Activity: Examination
MITF (Microphthalmia associated transcription factor) is a bHLH-Zip transcription factor, necessary for the development and function of melanocytes in the skin and hair. It is also necessary for normal development of the pigment cells of the eye (retinal pigment epithelial cells) and is therefore important for the development of the vertebrate eye. Recently, it has been shown that MITF is also necessary for the maintenance of melanoma cells where it acts as a lineage survival oncogene. The thesis is divided into three parts and shows that: 1) Not only is the structure of the Mitf gene conserved between vertebrates and the fruitfly, but also its function is conserved with respect to eye development. The role of Mitf is to ensure that the cells adjacent to the neural cells in the eye (RPE cells in vertebrates, peripodial cells in Drosophila), acquire a non-neural fate. 2) The Mitf gene is well conserved, not only with respect to exons but also in the promoter and the 3´UTR region. The 3´UTR region is over 3 kb long in the mouse and has 35% conservation in 11 vertebrate species. These conserved areas contain microRNA (miRNA) binding sites. 3) The miRNA binding sites in the 3´UTR region of the MITF gene are important for regulating the amount of MITF mRNA in melanoma cells. This is potentially a very important way to limit MITF mRNA in these cells and even to eliminate it altogether in melanoma cells. The results presented here show a very high conservation of the Mitf gene, both considering its structure and function. In addition, we show that the miRNAs miR-148 and miR-137 can regulate MITF expression in melanoma cells.