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Direct protein-protein interaction of 11 beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase in the endoplasmic reticulum lumen

Atanasov, Atanas G. and Nashev, Lyubomir G. and Gelman, Laurent and Legeza, Balazs and Sack, Ragna and Portmann, Reto and Odermatt, Alex. (2008) Direct protein-protein interaction of 11 beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase in the endoplasmic reticulum lumen. Biochimica et biophysica acta. Molecular cell research, Vol. 1783, Issue 8. pp. 1536-1543.

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Official URL: http://edoc.unibas.ch/dok/A5248816

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Abstract

Hexose-6-phosphate dehydrogenase (H6PDH) has been shown to stimulate 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1)-dependent local regeneration of active glucocorticoids. Here, we show that coexpression with H6PDH results in a dramatic shift from 11 beta-HSD1 oxidase to reductase activity without affecting the activity of the endoplasmic reticular enzyme 17 beta-HSD2. Immunoprecipitation experiments revealed coprecipitation of H6PDH with 11 beta-HSD1 but not with the related enzymes 11 beta-HSD2 and 17 beta-HSD2, suggesting a specific interaction between H6PDH and 11 beta-HSD1. The use of the 11 beta-HSD1/11 beta-HSD2 chimera indicates that the N-terminal 39 residues of 11 beta-HSD1 are sufficient for interaction with H6PDH. An important role of the N-terminus was indicated further by the significantly stronger interaction of 11 beta-HSD1 mutant Y18-21A with H6PDH compared to wild-type 11 beta-HSD1. The protein-protein interaction and the involvement of the N-terminus of 11 beta-HSD1 were confirmed by Far-Western blotting. Finally, fluorescence resonance energy transfer (FRET) measurements of HEK-293 cells expressing fluorescently labeled proteins provided evidence for an interaction between 11 beta-HSD1 and H6PDH in intact cells. Thus, using three different methods, we provide strong evidence that the functional coupling between 11 beta-HSD1 and H6PDH involves a direct physical interaction of the two proteins. (C) 2008 Elsevier B.V. All rights reserved.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
UniBasel Contributors:Odermatt, Alex and Nashev, Lyubomir Georgiev and Legeza, Balazs
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier Science
ISSN:0006-3002
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:29
Deposited On:22 Mar 2012 14:10

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