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dc.creatorChachami, G.en
dc.creatorParaskeva, E.en
dc.creatorMingot, J. M.en
dc.creatorBraliou, G. G.en
dc.creatorGorlich, D.en
dc.creatorSimos, G.en
dc.date.accessioned2015-11-23T10:24:23Z
dc.date.available2015-11-23T10:24:23Z
dc.date.issued2009
dc.identifier10.1016/j.bbrc.2009.09.093
dc.identifier.issn0006-291X
dc.identifier.urihttp://hdl.handle.net/11615/26537
dc.description.abstractHypoxia-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-1 alpha contains a C-terminal bipartite basic NLS that interacts with importins alpha. We have recently shown that HIF-1 alpha 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-1 alpha can still enter the nucleus when CRM1-dependent nuclear export is inhibited, indicating that HIF-1 alpha 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-1 alpha more efficiently than the classical importin alpha/beta NLS receptor. Binding assays confirmed the specific physical interaction between HIF-1 alpha and importins 4 and 7. Moreover, the interaction of importin 7 with HIF-1 alpha 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-1 alpha nuclear accumulation and activity. Taken together, our data show that shuttling of HIF-1 alpha. between cytoplasm and nucleus is a complex process involving several members of the nuclear transport receptor family. (C) 2009 Elsevier Inc. All rights reserved.en
dc.sourceBiochemical and Biophysical Research Communicationsen
dc.source.uri<Go to ISI>://WOS:000271552400012
dc.subjectHIF-1en
dc.subjectHypoxiaen
dc.subjectNuclear importen
dc.subjectImportin 4en
dc.subjectImportin 7en
dc.subjectIMMUNODEFICIENCY-VIRUS TYPE-1en
dc.subjectSIGNAL-TRANSDUCTIONen
dc.subjectMULTIPLE PATHWAYSen
dc.subjectRECEPTORen
dc.subjectTRANSLOCATIONen
dc.subjectLOCALIZATIONen
dc.subjectEXPORTen
dc.subjectBETAen
dc.subjectHYPOXIA-INDUCIBLE-FACTOR-1-ALPHAen
dc.subjectHYDROXYLASESen
dc.subjectBiochemistry & Molecular Biologyen
dc.subjectBiophysicsen
dc.titleTransport of hypoxia-inducible factor HIF-1 alpha into the nucleus involves importins 4 and 7en
dc.typejournalArticleen


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