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http://purl.uniprot.org/citations/9822602http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9822602http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9822602http://www.w3.org/2000/01/rdf-schema#comment"In response to decreased cellular oxygen concentrations the basic helix-loop-helix (bHLH)/PAS (Per, Arnt, Sim) hypoxia-inducible transcription factor, HIF-1alpha, mediates activation of networks of target genes involved in angiogenesis, erythropoiesis and glycolysis. Here we demonstrate that the mechanism of activation of HIF-1alpha is a multi-step process which includes hypoxia-dependent nuclear import and activation (derepression) of the transactivation domain, resulting in recruitment of the CREB-binding protein (CBP)/p300 coactivator. Inducible nuclear accumulation was shown to be dependent on a nuclear localization signal (NLS) within the C-terminal end of HIF-1alpha which also harbors the hypoxia-inducible transactivation domain. Nuclear import of HIF-1alpha was inhibited by either deletion or a single amino acid substitution within the NLS sequence motif and, within the context of the full-length protein, these mutations also resulted in inhibition of the transactivation activity of HIF-1alpha and recruitment of CBP. However, nuclear localization per se was not sufficient for transcriptional activation, since fusion of HIF-1alpha to the heterologous GAL4 DNA-binding domain generated a protein which showed constitutive nuclear localization but required hypoxic stimuli for function as a CBP-dependent transcription factor. Thus, hypoxia-inducible nuclear import and transactivation by recruitment of CBP can be functionally separated from one another and play critical roles in signal transduction by HIF-1alpha."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.org/dc/terms/identifier"doi:10.1093/emboj/17.22.6573"xsd:string
http://purl.uniprot.org/citations/9822602http://purl.org/dc/terms/identifier"doi:10.1093/emboj/17.22.6573"xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"Okamoto K."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"Okamoto K."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"Tanaka H."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"Tanaka H."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"Makino Y."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"Makino Y."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"Kallio P.J."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"Kallio P.J."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"O'Brien S."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"O'Brien S."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"Poellinger L."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"Poellinger L."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"Carrero P."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/author"Carrero P."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/date"1998"xsd:gYear
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/date"1998"xsd:gYear
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/name"EMBO J."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/name"EMBO J."xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/pages"6573-6586"xsd:string
http://purl.uniprot.org/citations/9822602http://purl.uniprot.org/core/pages"6573-6586"xsd:string