Nucleocytoplasmic Shuttling of Steroid Receptors

Abstract

Publisher Summary This chapter elaborates the nucleocytoplasmic shuttling of steroid receptors. The activity of various steroid receptors hormone-independent nuclear localization signal sequences (NLSs) is suppressed, in cis, by the unoccupied glucocorticoid receptors ligand binding domain (GR LBD). This repressive function is relieved upon the binding of hormone, most likely reflecting exposure of the NLS from a site within a receptor heteromeric complex. In some cells, heat-shock protein (hsp)70 appears to remain bound to GR following its activation and tight association with nuclei, prompting speculation that hsp70 may influence some nuclear functions of the receptor or directly participate in the nuclear transport of GR. Analogous effects on GR nuclear retention were also observed in nontransformed NRK cells treated with okadaic acid, a specific inhibitor of protein phosphatase types 1 and 2A. The nucleocytoplasmic shuttling of other steroid receptors could likewise be influenced by their association in nuclear anchoring complexes, while still accounting for the unique equilibrium subcellular distributions observed among different receptors. The reformation of a GR heteromeric complex could represent the ATP-dependent step that has been postulated to be required for GR recycling and perhaps for nuclear export.