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- W3133562272 endingPage "119000" @default.
- W3133562272 startingPage "119000" @default.
- W3133562272 abstract "A dimer of the heat-shock protein of 90-kDa (Hsp90) represents the critical core of the chaperone complex associated to the glucocorticoid receptor (GR) oligomer. The C-terminal end of the Hsp90 dimer shapes a functional acceptor site for co-chaperones carrying tetratricopeptide repeat (TPR) domains, where they bind in a mutually exclusive and competitive manner. They impact on the biological properties of the GR•Hsp90 complex and are major players of the GR transport machinery. Recently, we showed that the overexpression of a chimeric TPR peptide influences the subcellular distribution of GR. In this study, the functional role of endogenous proteins carrying TPR or TPR-like sequences on GR subcellular distribution was characterized. It is demonstrated that, contrarily to the positive influence of FKBP52 on GR nuclear accumulation, FKBP51 and 14-3-3 impaired this property. While SGT1α showed no significant effect, the overexpression of the Ser/Thr phosphatase PP5 resulted in a nearly equal nuclear-cytoplasmic redistribution of GR rather than its typical cytoplasmic localization in the absence of steroid. This observation led to analyse the influence of the phosphorylation status of GR, which resulted not linked to its nucleo-cytoplasmic shuttling mechanism. Nonetheless, it was evidenced that both PP5 and FKBP52 are related to the anchorage of the GR to nucleoskeleton structures. The influence of these TPR domain proteins on the steroid-dependent transcriptional activity of GR was also characterized. It is postulated that the pleiotropic actions of the GR in different cell types may be the consequence of the relative abundance of different TPR-domain interacting co-chaperones." @default.
- W3133562272 created "2021-03-15" @default.
- W3133562272 creator A5018147991 @default.
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- W3133562272 date "2021-05-01" @default.
- W3133562272 modified "2023-10-06" @default.
- W3133562272 title "Differential regulation of the glucocorticoid receptor nucleocytoplasmic shuttling by TPR-domain proteins" @default.
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- W3133562272 doi "https://doi.org/10.1016/j.bbamcr.2021.119000" @default.
- W3133562272 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33675851" @default.
- W3133562272 hasPublicationYear "2021" @default.
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