at Google ScholarTitle 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
(2007)
Issue 2
.
- pp. 199-205.
ISSN 1470-8728
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: | 20 Apr 2022 10:50 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/10143 |