Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/27499
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
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 1083-351X |
Organisation: | Centre for the Molecular Genetics of Development |
Statement of Responsibility: | 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 Animals Humans Mice Trans-Activators 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: | http://www.jbc.org/cgi/content/abstract/280/14/14240 |
Appears in Collections: | Aurora harvest 6 Centre for the Molecular Genetics of Development publications Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.