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https://hdl.handle.net/2440/27499
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dc.contributor.author | Bracken, C. | - |
dc.contributor.author | Whitelaw, M. | - |
dc.contributor.author | Peet, D. | - |
dc.date.issued | 2005 | - |
dc.identifier.citation | Journal of Biological Chemistry, 2005; 280(14):14240-14251 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.issn | 1083-351X | - |
dc.identifier.uri | http://hdl.handle.net/2440/27499 | - |
dc.description | © 2004 by The American Society for Biochemistry and Molecular Biology | - |
dc.description.abstract | The hypoxia-inducible factors 1α (HIF-1α) and 2α (HIF-2α) are key regulators of the transcriptional response to low oxygen and are closely related in domain architecture, DNA binding, and activation mechanisms. Despite these similarities, targeted disruption of the HIF- α genes in mice results in distinctly different phenotypes demonstrating nonredundancy of function, although the underlying mechanisms remain unclear. Here we report on the novel and specific interaction of HIF-2α, but not HIF-1α, with the NF- κB essential modulator (NEMO) using immunoprecipitation, mammalian two-hybrid, and in vitro protein interaction assays. Reporter gene assays demonstrate that this interaction specifically enhances normoxic HIF-2α transcriptional activity, independently of the HIF-2α transactivation domain, consistent with a model by which NEMO aids CBP/p300 recruitment to HIF-2α. In contrast, HIF-2α overexpression does not alter NF- κB signaling, suggesting that the functional consequence of the HIF-2α /NEMO interaction is limited to the HIF pathway. The specificity of NEMO for HIF-2α represents one of the few known differential protein-protein interactions between the HIF-α proteins, which has important implications for the activity of HIF-2α and is also the first postulated NF-κ B-independent role for NEMO. | - |
dc.description.statementofresponsibility | Cameron P. Bracken, Murray L. Whitelaw and Daniel J. Peet | - |
dc.language.iso | en | - |
dc.publisher | Amer Soc Biochemistry Molecular Biology Inc | - |
dc.source.uri | http://www.jbc.org/cgi/content/abstract/280/14/14240 | - |
dc.subject | Cell Line | - |
dc.subject | Animals | - |
dc.subject | Humans | - |
dc.subject | Mice | - |
dc.subject | Trans-Activators | - |
dc.subject | Nuclear Proteins | - |
dc.subject | Recombinant Fusion Proteins | - |
dc.subject | Transcription Factors | - |
dc.subject | Oligonucleotides, Antisense | - |
dc.subject | Two-Hybrid System Techniques | - |
dc.subject | Signal Transduction | - |
dc.subject | Transcription, Genetic | - |
dc.subject | Gene Expression Regulation | - |
dc.subject | Genes, Reporter | - |
dc.subject | E1A-Associated p300 Protein | - |
dc.subject | I-kappa B Kinase | - |
dc.subject | Basic Helix-Loop-Helix Transcription Factors | - |
dc.subject | Hypoxia-Inducible Factor 1, alpha Subunit | - |
dc.subject | Protein Serine-Threonine Kinases | - |
dc.title | Activity of hypoxia-inducible factor 2α is regulated by association with the NF-κB essential modulator | - |
dc.title.alternative | Activity of hypoxia-inducible factor 2alpha is regulated by association with the NF-kappaB essential modulator | - |
dc.type | Journal article | - |
dc.contributor.organisation | Centre for the Molecular Genetics of Development | - |
dc.identifier.doi | 10.1074/jbc.M409987200 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Peet, D. [0000-0002-6085-8936] | - |
Appears in Collections: | Aurora harvest 6 Centre for the Molecular Genetics of Development publications Molecular and Biomedical Science publications |
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