| Transport of hypoxia-inducible factor HIF-1alpha into the nucleus involves importins 4 and 7. | |
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MedLine Citation:
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PMID: 19788888 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hypoxia-inducible transcription factor 1 (HIF-1) mediates the cellular response to hypoxia. HIF-1 activity is controlled via the synthesis, degradation or intracellular localization of its alpha subunit. HIF-1alpha contains a C-terminal bipartite basic NLS that interacts with importins alpha. We have recently shown that HIF-1alpha also contains an atypical hydrophobic CRM1- and phosphorylation-dependent NES and can therefore shuttle in and out of the nucleus. We now report that C-terminal NLS mutants of HIF-1alpha can still enter the nucleus when CRM1-dependent nuclear export is inhibited, indicating that HIF-1alpha contains an additional functional nuclear import signal. Using an in vitro nuclear import assay, we further show that importins 4 and 7 accomplish nuclear import of HIF-1alpha more efficiently than the classical importin alpha/beta NLS receptor. Binding assays confirmed the specific physical interaction between HIF-1alpha and importins 4 and 7. Moreover, the interaction of importin 7 with HIF-1alpha is mapped at its N-terminal part encompassing the bHLH-PAS(A) domain. By expressing functional HIF-1 in yeast, we show that Nmd5, the yeast orthologue of importin 7, is required for HIF-1alpha nuclear accumulation and activity. Taken together, our data show that shuttling of HIF-1alpha between cytoplasm and nucleus is a complex process involving several members of the nuclear transport receptor family. |
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Authors:
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Georgia Chachami; Efrosyni Paraskeva; José-Manuel Mingot; Georgia G Braliou; Dirk Görlich; George Simos |
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Publication Detail:
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Type: Journal Article Date: 2009-09-27 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 390 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-10-26 Completed Date: 2009-11-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 235-40 Citation Subset: IM |
Affiliation:
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Laboratory of Biochemistry, School of Medicine, University of Thessaly, Mezourlo, 41110 Larissa, Greece. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus Cell Nucleus / metabolism* Cytoplasm / metabolism Hela Cells Humans Hypoxia-Inducible Factor 1, alpha Subunit / genetics, metabolism* Karyopherins / genetics, metabolism* Membrane Transport Proteins / genetics, metabolism* Receptors, Cytoplasmic and Nuclear / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/HIF1A protein, human; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/IPO7 protein, human; 0/Karyopherins; 0/Membrane Transport Proteins; 0/Receptors, Cytoplasmic and Nuclear; 0/importin 4, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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