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Title

Nucleocytoplasmic shuttling of the glucocorticoid receptor is influenced by tetratricopeptide repeat-containing proteins

Authors
Mazaira, Gisela I.
Galigniana, Mario D.
Published in Journal of Cell Science. 2020, vol. 133, no. jcs238873, p. 1-12
Abstract It has been demonstrated that tetratricopeptide-repeat (TPR) domain proteins regulate the subcellular localization of glucocorticoid receptor (GR). This study analyses the influence of the TPR domain of high molecular weight immunophilins in the retrograde transport and nuclear retention of GR. Overexpression of the TPR peptide prevented efficient nuclear accumulation of the GR by disrupting the formation of complexes with the dynein-associated immunophilin FKBP52 (also known as FKBP4), the adaptor transporter importin-β1 (KPNB1), the nuclear pore-associated glycoprotein Nup62 and nuclear matrix-associated structures. We also show that nuclear import of GR was impaired, whereas GR nuclear export was enhanced. Interestingly, the CRM1 (exportin-1) inhibitor leptomycin-B abolished the effects of TPR peptide overexpression, although the drug did not inhibit GR nuclear export itself. This indicates the existence of a TPRdomain- dependent mechanism for the export of nuclear proteins. The expression balance of those TPR domain proteins bound to the GR–Hsp90 complex may determine the subcellular localization and nucleocytoplasmic properties of the receptor, and thereby its pleiotropic biological properties in different tissues and cell types.
Keywords Glucocorticoid receptorTetratricopeptide repeatsImmunophilinsFKBP52Hsp90Nuclear matrix
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Article (Published version) (6.5 MB) - document accessible for UNIGE members only Limited access to UNIGE (until 2021-07-02)
Other version: http://jcs.biologists.org/lookup/doi/10.1242/jcs.238873
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Research group Groupe Picard
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MAZAIRA, Gisela I., ECHEVERRIA, Pablo, GALIGNIANA, Mario D. Nucleocytoplasmic shuttling of the glucocorticoid receptor is influenced by tetratricopeptide repeat-containing proteins. In: Journal of Cell Science, 2020, vol. 133, n° jcs238873, p. 1-12. doi: 10.1242/jcs.238873 https://archive-ouverte.unige.ch/unige:138332

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Deposited on : 2020-07-10

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