Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/27998
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lando, D. | - |
dc.contributor.author | Pongratz, I. | - |
dc.contributor.author | Poellinger, L. | - |
dc.contributor.author | Whitelaw, M. | - |
dc.date.issued | 2000 | - |
dc.identifier.citation | Journal of Biological Chemistry, 2000; 275(7):4618-4627 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.issn | 1083-351X | - |
dc.identifier.uri | http://hdl.handle.net/2440/27998 | - |
dc.description.abstract | Hypoxia-inducible factor 1α (HIF-1α) and the HIF-like factor (HLF) are two highly related basic Helix-Loop-Helix/Per-Arnt-Sim (bHLH/PAS) homology transcription factors that undergo dramatically increased function at low oxygen levels. Despite strong similarities in their activation mechanisms (e.g. they both undergo rapid hypoxia-induced protein stabilization, bind identical target DNA sequences, and induce synthetic reporter genes to similar degrees), they are both essential for embryo survival via distinct functions during vascularization (HIF-1α) or catecholamine production (HLF). It is currently unknown how such specificity of action is achieved. We report here that DNA binding by HLF, but not by HIF-1α, is dependent upon reducing redox conditions. In vitro DNA binding and mammalian two-hybrid assays showed that a unique cysteine in the DNA-binding basic region of HLF is a target for the reducing activity of redox factor Ref-1. Although the N-terminal DNA-binding domain of HIF-1α can function in the absence of Ref-1, we found that the C-terminal region containing the transactivation domain requires Ref-1 for full activity. Our data reveal that the hypoxia-inducible factors are subject to complex redox control mechanisms that can target discrete regions of the proteins and are the first to establish a discriminating control mechanism for differential regulation of HIF-1α and HLF activity. | - |
dc.language.iso | en | - |
dc.publisher | Amer Soc Biochemistry Molecular Biology Inc | - |
dc.source.uri | http://www.jbc.org/cgi/content/abstract/275/7/4618 | - |
dc.subject | Hela Cells | - |
dc.subject | Humans | - |
dc.subject | Cysteine | - |
dc.subject | DNA-(Apurinic or Apyrimidinic Site) Lyase | - |
dc.subject | Carbon-Oxygen Lyases | - |
dc.subject | Serine | - |
dc.subject | DNA-Binding Proteins | - |
dc.subject | Nuclear Proteins | - |
dc.subject | Recombinant Proteins | - |
dc.subject | Transcription Factors | - |
dc.subject | Oligonucleotides, Antisense | - |
dc.subject | DNA | - |
dc.subject | Mutagenesis, Site-Directed | - |
dc.subject | Gene Expression Regulation | - |
dc.subject | Amino Acid Sequence | - |
dc.subject | Helix-Loop-Helix Motifs | - |
dc.subject | Sequence Homology, Amino Acid | - |
dc.subject | Oxidation-Reduction | - |
dc.subject | Molecular Sequence Data | - |
dc.subject | Hypoxia-Inducible Factor 1 | - |
dc.subject | Hypoxia-Inducible Factor 1, alpha Subunit | - |
dc.title | A redox mechanism controls differential DNA binding activities of hypoxia-inducible factor (HIF) 1a and the HIF-like factor | - |
dc.type | Journal article | - |
dc.contributor.organisation | Centre for the Molecular Genetics of Development | - |
dc.identifier.doi | 10.1074/jbc.275.7.4618 | - |
pubs.publication-status | Published | - |
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.