التفاصيل البيبلوغرافية
| العنوان: |
Domain mapping on the human metastasis regulator protein h-Prune reveals a C-terminal dimerization domain. |
| المؤلفون: |
Sabine Middelhaufe, Livia Garzia, Uta-Maria Ohndorf, Barbara Kachholz, Massimo Zollo, Clemens Steegborn |
| المصدر: |
Biochemical Journal; 2007, Vol. 407 Issue 2, p199-205, 7p |
| مصطلحات موضوعية: |
GENE mapping, CANCER cells, BREAST cancer, METASTASIS, PROTEOLYSIS |
| مستخلص: |
The human orthologue of the Drosophila prune protein (h-Prune) is an interaction partner and regulator of the metastasis suppressor protein NM23-H1 (non-metastatic protein 23). Studies on a cellular breast-cancer model showed that inhibition of the cAMP-specific PDE (phosphodiesterase) activity of h-Prune lowered the incidence of metastasis formation, suggesting that inhibition of h-Prune could be a therapeutic approach towards metastatic tumours. H-Prune shows no sequence similarity with known mammalian PDEs, but instead appears to belong to the DHH (Asp-His-His) superfamily of phosphoesterases. In order to investigate the structure and molecular function of h-Prune, we expressed recombinant h-Prune in a bacterial system. Through sequence analysis and limited proteolysis, we identified domain boundaries and a potential coiled-coil region in a C-terminal cortexillin homology domain. We found that this C-terminal domain mediated h-Prune homodimerization, as well as its interaction with NM23-H1. The PDE catalytic domain of h-Prune was mapped to the N-terminus and shown to be active, even when present in a monomeric form. Our findings indicate that h-Prune is composed of two independent active sites and two interaction sites for the assembly of oligomeric signalling complexes. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
