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PMID: 15004228 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Importin 7 and importin alpha/importin beta are nuclear import receptors for the glucocorticoid receptor.

Molecular biology of the cell ·Vol. 15 ·No. 5 ·2004-05-00 ·Pages 2276-86

Freedman ND, Yamamoto KR

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 alpha selectively bound NL1. In an in vitro nuclear import assay, both importin 7 and the importin alpha-importin beta 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 alpha bound GR even in the absence of hormone; thus, hormonal control of localization is exerted at a step downstream of import receptor binding.

MeSH Terms
Active Transport, Cell Nucleus Amino Acid Sequence Animals Cell Line Cell Nucleus/physiology,ultrastructure Dexamethasone/pharmacology Green Fluorescent Proteins/analysis Humans Karyopherins Molecular Sequence Data Nuclear Localization Signals Nuclear Proteins/genetics,metabolism Protein Binding Rats Receptors, Glucocorticoid/chemistry,genetics,metabolism Saccharomyces cerevisiae/genetics,metabolism,ultrastructure Saccharomyces cerevisiae Proteins/genetics,metabolism alpha Karyopherins/metabolism beta Karyopherins/metabolism
Chemicals
Karyopherins Nuclear Localization Signals Nuclear Proteins Receptors, Glucocorticoid SXM1 protein, S cerevisiae Saccharomyces cerevisiae Proteins alpha Karyopherins beta Karyopherins enhanced green fluorescent protein Green Fluorescent Proteins Dexamethasone
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Freedman Neal D
Department of Cellular and Molecular Pharmacology, University of California-San Francisco, San Francisco, CA 94143-2280, USA.
Yamamoto Keith R
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e03-11-0839
Published
2004-05-00
Epub
2004-00-05
Pages
2276-86
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC404022
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e03-11-0839 PMC Full Text View journal details
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