Oral communication, PS5 / C70
Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011
The Mitf structure unravels DNA binding and dimerization specificities
| SPEAKER | M.H. Ogmundsdottir #whois submiter ? |
| AUTHOR(s) | V. Pogenberg, M.H. Ogmundsdottir, K. Bergsteinsdottir, M. Milewski, V. Deineko, B. Phung, A. Schepsky, M. Wilmanns, E. Steingrimsson |
The microphthalmia-associated transcription factor (Mitf) is essential for normal melanocyte development and has also been shown to play an important role in melanoma where it acts as a lineage survival oncogene. Mitf plays multiple roles in melanocytes and melanoma cells by regulating the expression of genes involved in various different processes including survival, proliferation, migration and differentiation. It is, however, not clear how it performs these different tasks in the same cell type, although signalling and DNA-binding specificity have been proposed to play an important role. We have analysed the structure of the MITF protein using X-ray crystallography and classical DNA binding studies of both wild type and mutant MITF proteins. The structures reveal how MITF discriminates between its target sequences. In addition, they show an unusual mode of dimerization that may explain how MITF selects its dimerization partner. This has provided new insights into the mechanisms of Mitf-mediated transcription regulation.
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