Regulation of hypoxia-inducible factor-1alpha by NF-kappaB.

ABSTRACT: HIF (hypoxia-inducible factor) is the main transcription factor activated by low oxygen tensions. HIF-1alpha (and other alpha 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-1alpha stabilization is also found in non-hypoxic conditions through an unknown mechanism. In the present study, we demonstrate that NF-kappaB (nuclear factor kappaB) is a direct modulator of HIF-1alpha expression. The HIF-1alpha promoter is responsive to selective NF-kappaB subunits. siRNA (small interfering RNA) studies for individual NF-kappaB members revealed differential effects on HIF-1alpha mRNA levels, indicating th

SUBMITTER: van Uden P 

PROVIDER: S-EPMC2474706 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature