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

Title data

Middelhaufe, Sabine ; Garzia, Livia ; Ohndorf, Uta-Maria ; Kachholz, Barbara ; Zollo, Massimo ; Steegborn, Clemens:
Domain mapping on the human metastasis regulator protein h-Prune reveals a C-terminal dimerization domain.
In: Biochemical Journal. Vol. 407 (15 October 2007) Issue 2 . - pp. 199-205.
ISSN 0006-2936
DOI: https://doi.org/10.1042/BJ20070408

Abstract in another language

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.

Further data

Item Type: Article in a journal
Refereed: Yes
Additional notes: PubMed-ID: 10745004
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry > Chair Biochemistry - Univ.-Prof. Dr. Clemens Steegborn
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry
Result of work at the UBT: No
DDC Subjects: 500 Science > 540 Chemistry
Date Deposited: 14 Apr 2015 10:41
Last Modified: 14 Apr 2015 10:41
URI: https://eref.uni-bayreuth.de/id/eprint/10143