Researchers uncover molecular structure of master regulator central to melanoma

Published on December 1, 2012 at 1:57 AM · No Comments

Promising target for the development of novel drugs

With the X-ray vision of DESY's light source DORIS, a research team from Hamburg and Iceland has uncovered the molecular structure of a master regulator central to the most deadly form of skin cancer, melanoma. The results, published in the scientific journal "Genes & Development", throw new light on the workings of the so-called Microphthalmia-associated Transcription Factor MITF, that is not only connected to skin cancer, but also to a variety of hereditary diseases where the production of the skin pigment melanin is disturbed, and to certain aspects of ageing. "Our data could provide a rational basis for the development of tailor-made drugs targeting MITF", explains first author Vivian Pogenberg from the Hamburg branch of the European Molecular Biology Laboratory (EMBL). Deutsches Elektronen-Synchrotron DESY is the leading German accelerator centre and one of the leading in the world. Among other things, DESY develops and provides accelerator based light sources for research.

Melanoma is a malignant tumor of the cells that produce the skin pigment melanin, the melanocytes. It is not the most common form of skin cancer but the one with the greatest death toll by far: about 3 out of 4 skin cancer related deaths are caused by melanoma. Important for the development of melanoma are malfunctions of the Microphtalmia-associated Transcription Factor MITF. Transcription factors regulate which part of the DNA is read and transcribed into a blueprint for a protein within the cell. Only few parts of the DNA are active in each cell, and this activity also changes with time. MITF for instance activates the cell's machinery to turn the amino acid tyrosine into the pigment melanin.

But MITF also makes stem cells turn into melanocytes in the first place and controls cell proliferation and death in these cells. That's why MITF is called a master regulator. In fact, it also has functions in other cell types like mast cells of the immune system and bone eating osteoclasts. Mutations in MITF not only play a role in the development of skin cancer, but also cause severe genetic diseases like the Tietz and Waardenburg syndromes that lead to deafness, skin and hair pigmentation defects, abnormal eye anatomy and altered vision. The transcription factor also plays a role in our hair turning grey with age and other age-related pigmentation alterations.

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