HIF-1伪 protein is upregulated in HIF-2伪 depleted cells via enhanced translation

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• 作者：Kathrin Schulz¹ ; Larissa Milke¹ ; Daniela Rü ; bsamen ; Heidi Menrad ; Tobias Schmid ; ² ; ^{T.Schmid@biochem.uni-frankfurt.de} ; Bernhard Brü ; ne²
• 关键词：HIF ; hypoxia-inducible factor ; HuR ; human antigen R ; GAPDH ; glyceraldehyde-3-phosphate dehydrogenase ; pVHL ; von Hippel-Lindau protein ; BNIP3 ; BCL-2/adenovirus E1B 19-kDa interacting protein 3
• 刊名：FEBS Letters
• 出版年：2012
• 期刊代码：70_00145793
• 类别：bio
• 出版时间：4 June, 2012
• 卷：586
• 期：11
• 页码：1652-1657
• 文件大小：555 K

摘要

The hypoxia-inducible factors HIF-1 and HIF-2 are primarily regulated via stabilization of their respective 伪-subunits under hypoxic conditions. Previously, compensatory upregulation of one HIF-伪-subunit upon depletion of the other 伪-subunit was described, yet the underlying mechanism remained elusive. Here we provide evidence that enhanced HIF-1伪 protein expression in HIF-2伪 knockdown (k/d) cells neither results from elevated HIF-1伪 mRNA expression, nor from increased HIF-1伪 protein stability. Instead, we identify enhanced HIF-1伪 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-1伪 regulation in HIF-2伪 k/d cells.