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HIF‐1α protein is upregulated in HIF‐2α depleted cells via enhanced translation
Author(s) -
Schulz Kathrin,
Milke Larissa,
Rübsamen Daniela,
Menrad Heidi,
Schmid Tobias,
Brüne Bernhard
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.04.039
Subject(s) - downregulation and upregulation , gene knockdown , protein subunit , microbiology and biotechnology , messenger rna , protein biosynthesis , translation (biology) , rna binding protein , chemistry , hypoxia (environmental) , protein stability , biology , biochemistry , apoptosis , gene , oxygen , organic chemistry
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.