Importin 7 and Importin α/Importin β Are Nuclear Import Receptors for the Glucocorticoid Receptor

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Abstract
The vertebrate glucocorticoid receptor (GR) is cytoplasmic without hormone and localizes to the nucleus after hormone binding. GR has two nuclear localization signals (NLS): NL1 is similar in sequence to the SV40 NLS; NL2 is poorly defined, residing in the ligand-binding domain. We found that GR displayed similar hormone-regulated compartmentalization in Saccharomyces cerevisiae and required the Sxm1 nuclear import receptor for NL2-mediated import. Two metazoan homologues of Sxm1, importin 7 and importin 8, bound both NL1 and NL2, whereas importin α selectively bound NL1. In an in vitro nuclear import assay, both importin 7 and the importin α-importin β heterodimer could import a GR NL1 fragment. Under these conditions, full-length GR localized to nuclei in the presence but not absence of an unidentified component in cell extracts. Interestingly, importin 7, importin 8, and importin α bound GR even in the absence of hormone; thus, hormonal control of localization is exerted at a step downstream of import receptor binding.