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

MAZAIRA, GISELA I.; ECHEVERRIA, PABLO C.; GALIGNIANA, MARIO D.

JOURNAL OF CELL SCIENCE

COMPANY OF BIOLOGISTS LTD

Año: 2020 vol. 133

0021-9533

It has been demonstrated that tetratricopeptide-repeat (TPR) domainproteins regulate the subcellular localization of glucocorticoid receptor(GR). This study analyses the influence of the TPR domain of highmolecular weight immunophilins in the retrograde transport andnuclear retention of GR. Overexpression of the TPR peptideprevented efficient nuclear accumulation of the GR by disrupting theformation of complexes with the dynein-associated immunophilinFKBP52 (also known as FKBP4), the adaptor transporter importin-β1(KPNB1), the nuclear pore-associated glycoproteinNup62 and nuclearmatrix-associated structures. We also show that nuclear import of GRwas impaired whereas GRnuclear export was enhanced. Interestingly,the CRM1 (exportin-1) inhibitor leptomycin-B abolished the effects ofTPR peptide overexpression, although the drug did not inhibit the GRnuclear export itself. This indicates the existence of a TPR-domaindependentmechanism for the export of nuclear proteins. Theexpression balance of those TPR domain proteins bound to theGR?Hsp90 complex may determine the subcellular localization andnucleocytoplasmic properties of the receptor, and thereby itspleiotropic biological properties in different tissues or cell types.