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- Title
HIF-1α protein is upregulated in HIF-2α depleted cells via enhanced translation
- Authors
Schulz, Kathrin; Milke, Larissa; Rübsamen, Daniela; Menrad, Heidi; Schmid, Tobias; Brüne, Bernhard
- Abstract
Abstract: The hypoxia-inducible factors HIF-1 and HIF-2 are primarily regulated via stabilization of their respective α-subunits under hypoxic conditions. Previously, compensatory upregulation of one HIF-α-subunit upon depletion of the other α-subunit was described, yet the underlying mechanism remained elusive. Here we provide evidence that enhanced HIF-1α protein expression in HIF-2α knockdown (k/d) cells neither results from elevated HIF-1α mRNA expression, nor from increased HIF-1α protein stability. Instead, we identify enhanced HIF-1α translation as molecular mechanism. Moreover, we found elevated levels of the RNA-binding protein HuR and provide evidence that HuR is critical for the compensatory HIF-1α regulation in HIF-2α k/d cells.
- Subjects
HYPOXIA-inducible factors; MESSENGER RNA; GENE expression; CELLULAR control mechanisms; PROTEIN stability; MOLECULAR biology
- Publication
FEBS Letters, 2012, Vol 586, Issue 11, p1652
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2012.04.039