Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

H-prune, a new cyclic nucleotide phosphodiesterase, binds to nm23-H1, a metastasis suppressor protein. The overexpression of h-prune in the MDA-MB-435 breast carcinoma cell line causes a substantial decrease of cAMP, and an increase in cellular motility. This latest effect is correlated both to the h-prune phosphodiesterase activity and to the interaction between h-prune and nm23-H1 proteins. Understanding the molecular changes in tumor cells with an increased level of expression of h-prune might shed light on motility processes, which are the driving forces of the cells to move away from the primary tumor and to become metastatic. This report overview genes and pathways influenced by h-prune overexpression in a conventional breast cancer cellular model.
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PMID:Unraveling genes and pathways influenced by H-prune PDE overexpression: a model to study cellular motility. 1525 13

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.
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PMID:Domain mapping on the human metastasis regulator protein h-Prune reveals a C-terminal dimerization domain. 1765 25