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Type: Journal article
Title: Activity of hypoxia-inducible factor 2α is regulated by association with the NF-κB essential modulator
Other Titles: Activity of hypoxia-inducible factor 2alpha is regulated by association with the NF-kappaB essential modulator
Author: Bracken, C.
Whitelaw, M.
Peet, D.
Citation: Journal of Biological Chemistry, 2005; 280(14):14240-14251
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2005
ISSN: 0021-9258
Organisation: Centre for the Molecular Genetics of Development
Statement of
Cameron P. Bracken, Murray L. Whitelaw and Daniel J. Peet
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.
Keywords: Cell Line
Nuclear Proteins
Recombinant Fusion Proteins
Transcription Factors
Oligonucleotides, Antisense
Two-Hybrid System Techniques
Signal Transduction
Transcription, Genetic
Gene Expression Regulation
Genes, Reporter
E1A-Associated p300 Protein
I-kappa B Kinase
Basic Helix-Loop-Helix Transcription Factors
Hypoxia-Inducible Factor 1, alpha Subunit
Protein Serine-Threonine Kinases
Description: © 2004 by The American Society for Biochemistry and Molecular Biology
DOI: 10.1074/jbc.M409987200
Published version:
Appears in Collections:Aurora harvest 6
Centre for the Molecular Genetics of Development publications
Molecular and Biomedical Science publications

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