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Nuclear translocation of hypoxia-inducible factors (HIFs): involvement of the classical importin alpha/beta pathway

Item Type:Article
Title:Nuclear translocation of hypoxia-inducible factors (HIFs): involvement of the classical importin alpha/beta pathway
Creators Name:Depping, R. and Steinhoff, A. and Schindler, S.G. and Friedrich, B. and Fagerlund, R. and Metzen, E. and Hartmann, E. and Koehler, M.
Abstract:Hypoxia-inducible factors are the key elements in the essential process of oxygen homeostasis of vertebrate cells. Stabilisation and subsequent nuclear localisation of HIF-alpha subunits results in the activation of target genes such as vegf, epo and glut1. The passage of transcription factors e.g. HIF-1alpha into the nucleus through the nuclear pore complex is regulated by nuclear transport receptors. Therefore nucleocytoplasmic shuttling can regulate transcriptional activity by facilitating the cellular traffic of transcription factors between both compartments. Here, we report on the identification of specific interactions of hypoxia-inducible factors with nuclear transport receptors importin alpha/beta. HIF-1alpha, -1beta, and HIF-2alpha are binding to importin alpha1, alpha3, alpha5, and alpha7. The direct interaction of HIF-1alpha to alpha importins is dependent on a functional nuclear localisation signal within the C-terminal region of the protein. In contrast, the supposed N-terminal NLS is not effective. Our findings provide new insight into the mechanism of the regulation of nuclear transport of hypoxia-inducible factors.
Keywords:Hypoxia-Inducible Factor, HIF, Importin, Nuclear Transport, NLS, Oxygen Homeostasis
Source:Biochimica et Biophysica Acta - Molecular Cell Research
ISSN:0167-4889
Publisher:Elsevier (The Netherlands)
Volume:1783
Number:3
Page Range:394-404
Date:March 2008
Official Publication:https://doi.org/10.1016/j.bbamcr.2007.12.006
PubMed:View item in PubMed

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