Document Detail


Transport of hypoxia-inducible factor HIF-1alpha into the nucleus involves importins 4 and 7.
MedLine Citation:
PMID:  19788888     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Georgia Chachami; Efrosyni Paraskeva; José-Manuel Mingot; Georgia G Braliou; Dirk Görlich; George Simos
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Publication Detail:
Type:  Journal Article     Date:  2009-09-27
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  390     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-10-26     Completed Date:  2009-11-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  235-40     Citation Subset:  IM    
Affiliation:
Laboratory of Biochemistry, School of Medicine, University of Thessaly, Mezourlo, 41110 Larissa, Greece.
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MeSH Terms
Descriptor/Qualifier:
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:
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

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