Schmidt, Jennifer and Riechers, Alexander and Stoll, Raphael and Amann, Thomas and Fink, Florian and Spruss, Thilo and Gronwald, Wolfram and Koenig, Burkhard and Hellerbrand, Claus and Bosserhoff, Anja Katrin (2012) Targeting Melanoma Metastasis and Immunosuppression with a New Mode of Melanoma Inhibitory Activity (MIA) Protein Inhibition. PLOS ONE, 7 (5): e37941. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Melanoma is the most aggressive form of skin cancer, with fast progression and early dissemination mediated by the melanoma inhibitory activity (MIA) protein. Here, we discovered that dimerization of MIA is required for functional activity through mutagenesis of MIA which showed the correlation between dimerization and functional activity. We subsequently identified the dodecapeptide AR71, which prevents MIA dimerization and thereby acts as a MIA inhibitor. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy demonstrated the binding of AR71 to the MIA dimerization domain, in agreement with in vitro and in vivo data revealing reduced cell migration, reduced formation of metastases and increased immune response after AR71 treatment. We believe AR71 is a lead structure for MIA inhibitors. More generally, inhibiting MIA dimerization is a novel therapeutic concept in melanoma therapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MALIGNANT-MELANOMA; CELLS; EXPRESSION; MIGRATION; TRANSITION; SECRETION; INVASION; SPECTRA; FAMILY; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Pathologie Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 May 2020 09:22 |
| Last Modified: | 13 May 2020 09:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18712 |
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