Regulation of hypoxia inducible factor-1α by NF-κB.

Patrick van Uden , Niall S Kenneth , Sonia Rocha (1)

1 Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences

The Hypoxia Inducible Factor (HIF) is the main transcription factor activated by low oxygen tensions. HIF-1α (and other alpha subunits) is tightly controlled mostly at the protein level, through the concerted action of a class of enzymes called Prolyl Hydroxylases (PHD1, 2 and 3). Most of the knowledge on HIF derives from studies following hypoxic stress, however, HIF-1α stabilisation is also found in non-hypoxic conditions through an unknown mechanism. Here, we demonstrate that NF-κB is a direct modulator of HIF-1α expression. The HIF-1α promoter is responsive to selective NF-κB subunits. siRNA studies for individual NF-κB members revealed differential effects on HIF-1α mRNA levels, indicating that NF-κB can regulate basal HIF-1α expression. Finally, when endogenous NF-κB is induced by TNF-α treatment, HIF-1α levels also change in a NF-κB dependent manner. In conclusion, we find that NF-κB can regulate basal, TNF-α, and in certain circumstances the hypoxia induced HIF-1α.

Mots clés: Life Sciences

Patrick van Uden, Niall S Kenneth, Sonia Rocha. Regulation of hypoxia inducible factor-1α by NF-κB.. Biochemical Journal, 2008, 412 (3), pp.477-484. ⟨10.1042/BJ20080476⟩. ⟨hal-00478993⟩