The transcriptional activation function of the HIF-like factor requires phosphorylation at a conserved threonine.
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.
Gradin
Katarina
K
Department of Biomolecular Science, Graduate School of Life Science, Tohoku University, Sendai, 980-8578, Japan.
Takasaki
Chikahisa
C
Fujii-Kuriyama
Yoshiaki
Y
Sogawa
Kazuhiro
K
D000595:Amino Acid Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002478:Cells, Cultured; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry; D010766:Phosphorylation; D013329:Structure-Activity Relationship; D013912:Threonine / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D015533:Transcriptional Activation; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D013912:Threonine; D015534:Trans-Activators; D014157:Transcription Factors; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human