Regulation of hypoxia-inducible factor-1 alpha by NF-kappa B

Patrick van Uden, Niall S. Kenneth, Sonia Rocha (Lead / Corresponding author)

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    Abstract

    HIF (hypoxia-inducible factor) is the main transcription factor activated by low oxygen tensions. HIF-1 alpha (and other a subunits) is tightly controlled mostly at the protein level, through the concerted action of a class of enzymes called PHDs (prolyl hydroxylases) 1, 2 and 3. Most of the knowledge of HIF derives from studies following hypoxic stress; however, HIF-1 alpha stabilization is also found in non-hypoxic conditions through an unknown mechanism. In the present study, we demonstrate that NF-kappa B (nuclear factor kappa B) is a direct modulator of HIF-1 alpha expression. The HIF-1 alpha promoter is responsive to selective NF-kappa B subunits. siRNA (small interfering RNA) studies for individual NF-kappa B members revealed differential effects on HIF-1 alpha mRNA levels, indicating that NF-kappa B can regulate basal HIF-1 alpha expression. Finally, when endogenous NF-kappa B is induced by TNF alpha (tumour necrosis factor alpha) treatment, HIF-1 alpha levels also change in an NF-kappa B-dependent manner. In conclusion, we find that NF-kappa B can regulate basal TNF alpha and, in certain circumstances, the hypoxia-induced HIF-1 alpha.

    Original languageEnglish
    Pages (from-to)477-484
    Number of pages8
    JournalBiochemical Journal
    Volume412
    Issue number3
    DOIs
    Publication statusPublished - 15 Jun 2008

    Keywords

    • hypoxia
    • hypoxia-inducible factor 1 (HIF-1)
    • nuclear factor kappa B (NF-kappa B)
    • tumour necrosis factor (TNF)
    • TUMOR-NECROSIS-FACTOR
    • RESPONSIVE ELEMENT
    • FACTOR 1-ALPHA
    • OXYGEN
    • GENE
    • HIF-1-ALPHA
    • ACTIVATION
    • PROMOTER
    • IDENTIFICATION
    • TRANSCRIPTION

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