differential impact of tetratricopeptide repeat proteins on the steroid hormone receptors微分的影响tetratricopeptide重复类固醇激素受体蛋白.pdfVIP

Differential Impact of Tetratricopeptide Repeat Proteins on the Steroid Hormone Receptors ¨ 1 1 1 1 Jan-Philip Schulke , Gabriela Monika Wochnik , Isabelle Lang-Rollin , Nils Christian Gassen , Regina 1 1 2 1 Theresia Knapp , Barbara Berning , Alexander Yassouridis , Theo Rein * 1 Chaperone Research Group, Max Planck Institute of Psychiatry, Munich, Germany, 2 Biostatistics Group, Max Planck Institute of Psychiatry, Munich, Germany Abstract Background: Tetratricopeptide repeat (TPR) motif containing co-chaperones of the chaperone Hsp90 are considered control modules that govern activity and specificity of this central folding platform. Steroid receptors are paradigm clients of Hsp90. The influence of some TPR proteins on selected receptors has been described, but a comprehensive analysis of the effects of TPR proteins on all steroid receptors has not been accomplished yet. Methodology and Principal Findings: We compared the influence of the TPR proteins FK506 binding proteins 51 and 52, protein phosphatase-5, C-terminus of Hsp70 interacting protein, cyclophillin 40, hepatitis-virus-B X-associated protein-2, and tetratricopeptide repeat protein-2 on all six steroid hormone receptors in a homogeneous mammalian cell system. To be able to assess each cofactor’s effect on the transcriptional activity of on each steroid receptor we employed transient transfection in a reporter gene assay. In addition, we evaluated the interactions of the TPR proteins with the receptors and components of the Hsp90 chaperone heterocomplex by coimmunoprecipitation. In the functional assays, corticosteroid