The transcriptional activation function of the HIF-like factor requires phosphorylation at a conserved threonine - PubMed (original) (raw)

. 2002 Jun 28;277(26):23508-14.

doi: 10.1074/jbc.M201307200. Epub 2002 Apr 30.

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• PMID: 11983697
• DOI: 10.1074/jbc.M201307200

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The transcriptional activation function of the HIF-like factor requires phosphorylation at a conserved threonine

Katarina Gradin et al. J Biol Chem. 2002.

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Abstract

The hypoxia-inducible factor (HIF)-1alpha and the HIF-like factor (HLF) transcription factors are regulated at multiple levels including protein stabilization, nuclear import, and activation of transactivation, resulting in recruitment of coactivators such as the cAMP-response element-binding protein (CREB)-binding protein (CBP)/p300 and SRC-1. During low oxygen tension these proteins modulate a network of genes that are necessary for angiogenesis, erythropopoiesis, and glycolysis. We report here that the C-terminal transactivation domain of HLF is phosphorylated on multiple sites and that phosphorylation on threonine 844 of HLF is necessary for the transcriptional activation function of the protein independently of the hypoxia condition. Importantly, using the mammalian two-hybrid system we demonstrate that a substitution of threonine 844 to an alanine decreased the enhanced transcriptional activation function mediated by CBP/p300.

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