Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition
Schmidt J, Riechers A, Stoll R, Amann T, Fink F, Spruss T, Gronwald W, Koenig B, Hellerbrand C, Bosserhoff AK (2012)
Publication Type: Journal article
Publication year: 2012
Journal
Book Volume: 7
Article Number: e37941
Journal Issue: 5
DOI: 10.1371/journal.pone.0037941
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. © 2012 Schmidt et al.
Authors with CRIS profile
Involved external institutions
Universität Regensburg
Germany (DE)
Ruhr-Universität Bochum (RUB)
Germany (DE)
Universitätsklinikum Regensburg
Germany (DE)
Germany (DE)
Ruhr-Universität Bochum (RUB)
Germany (DE)
Universitätsklinikum Regensburg
Germany (DE)
How to cite
APA:
Schmidt, J., Riechers, A., Stoll, R., Amann, T., Fink, F., Spruss, T.,... Bosserhoff, A.K. (2012). Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition. PLoS ONE, 7(5). https://doi.org/10.1371/journal.pone.0037941
MLA:
Schmidt, Jennifer, et al. "Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition." PLoS ONE 7.5 (2012).
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