dc.creator | Chachami, G. | en |
dc.creator | Paraskeva, E. | en |
dc.creator | Mingot, J. M. | en |
dc.creator | Braliou, G. G. | en |
dc.creator | Gorlich, D. | en |
dc.creator | Simos, G. | en |
dc.date.accessioned | 2015-11-23T10:24:23Z | |
dc.date.available | 2015-11-23T10:24:23Z | |
dc.date.issued | 2009 | |
dc.identifier | 10.1016/j.bbrc.2009.09.093 | |
dc.identifier.issn | 0006-291X | |
dc.identifier.uri | http://hdl.handle.net/11615/26537 | |
dc.description.abstract | 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-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.source | Biochemical and Biophysical Research Communications | en |
dc.source.uri | <Go to ISI>://WOS:000271552400012 | |
dc.subject | HIF-1 | en |
dc.subject | Hypoxia | en |
dc.subject | Nuclear import | en |
dc.subject | Importin 4 | en |
dc.subject | Importin 7 | en |
dc.subject | IMMUNODEFICIENCY-VIRUS TYPE-1 | en |
dc.subject | SIGNAL-TRANSDUCTION | en |
dc.subject | MULTIPLE PATHWAYS | en |
dc.subject | RECEPTOR | en |
dc.subject | TRANSLOCATION | en |
dc.subject | LOCALIZATION | en |
dc.subject | EXPORT | en |
dc.subject | BETA | en |
dc.subject | HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA | en |
dc.subject | HYDROXYLASES | en |
dc.subject | Biochemistry & Molecular Biology | en |
dc.subject | Biophysics | en |
dc.title | Transport of hypoxia-inducible factor HIF-1 alpha into the nucleus involves importins 4 and 7 | en |
dc.type | journalArticle | en |