Unsaturated fatty acids as high-affinity ligands of the C-terminal Per-ARNT-Sim domain from the Hypoxia-inducible factor 3[alpha]

Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia. The oxygen-dependent stability and activity of the HIF-α subunits is traditionally associated to post-translational modifications such as hydroxylation, acetylation, ubiquitination, and...

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Bibliographic Details
Published in:Scientific reports 2015-08, Vol.5, p.12698
Main Authors: Fala, Angela M, Oliveira, Juliana F, Adamoski, Douglas, Aricetti, Juliana A, Dias, Marilia M, Dias, Marcio V B, Sforça, Maurício L, Lopes-de-oliveira, Paulo S, Rocco, Silvana A, Caldana, Camila, Dias, Sandra M G, Ambrosio, Andre L B
Format: Article
Language:English
Subjects:
Acetylation
Fatty acids
Hydroxylation
Hypoxia
Hypoxia-inducible factors
Ligands
Phosphorylation
Post-translation
Transcription factors
Ubiquitination
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Summary:Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia. The oxygen-dependent stability and activity of the HIF-α subunits is traditionally associated to post-translational modifications such as hydroxylation, acetylation, ubiquitination, and phosphorylation. Here we report novel evidence showing that unsaturated fatty acids are naturally occurring, non-covalent structural ligands of HIF-3α, thus providing the initial framework for exploring its exceptional role as a lipid sensor under hypoxia.
ISSN:2045-2322
DOI:10.1038/srep12698