Differential Impact of Tetratricopeptide Repeat Proteins on the Steroid Hormone Receptors 英文参考文献.docVIP

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Differential Impact of Tetratricopeptide Repeat Proteins on the Steroid Hormone Receptors 英文参考文献.doc

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Differential Impact of Tetratricopeptide Repeat Proteins on the Steroid Hormone Receptors 英文参考文献

DifferentialImpactofTetratricopeptideRepeatProteins ontheSteroidHormoneReceptors Jan-PhilipSchu¨lke1,GabrielaMonikaWochnik1,IsabelleLang-Rollin1,NilsChristianGassen1 ,Regina TheresiaKnapp1,BarbaraBerning1,AlexanderYassouridis2,TheoRein1* 1ChaperoneResearchGroup,MaxPlanckInstituteofPsychiatry,Munich,Germany,2BiostatisticsGroup,MaxPlanckInstituteofPsychiatry,Munich,Germany Abstract Background: Tetratricopeptide repeat (TPR) motif containing co-chaperones of the chaperone Hsp90 are considered controlmodulesthatgovernactivityandspecificityofthiscentralfoldingplatform.Steroidreceptorsareparadigmclientsof Hsp90.TheinfluenceofsomeTPRproteinsonselectedreceptorshasbeendescribed,butacomprehensiveanalysisofthe effectsofTPRproteinsonallsteroidreceptorshasnotbeenaccomplishedyet. MethodologyandPrincipalFindings:WecomparedtheinfluenceoftheTPRproteinsFK506bindingproteins51and52, protein phosphatase-5, C-terminus ofHsp70interacting protein, cyclophillin 40,hepatitis-virus-B X-associated protein-2, andtetratricopeptide repeat protein-2 onallsixsteroid hormone receptors inahomogeneous mammalian cellsystem. To be able to assess each cofactor’s effect on the transcriptional activity of on each steroid receptor we employed transient transfection in areporter gene assay. Inaddition, we evaluated the interactions of the TPR proteins with the receptors andcomponents oftheHsp90chaperone heterocomplex bycoimmunoprecipitation. Inthefunctional assays, corticosteroid and progesterone receptors displayed the most sensitive and distinct reaction to the TPR proteins. Androgen receptor’s activity was moderately impaired bymost cofactors, whereas the Estrogen receptors’ activity was impaired by most cofactors only to a minor degree. Second, interaction studies revealed that the strongly receptor- interacting co-chaperones were all among the inhibitory proteins. Intriguingly, the TPR-proteins also differentially co- precipitated theheterochaperone complex components Hsp90, Hsp70, andp23,pointing