Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation.
Hypoxia-inducible factor 1 (HIF-1) plays a central role in cellular adaptation to changes in oxygen availability. Recently, prolyl hydroxylation was identified as a key regulatory event that targets the HIF-1alpha subunit for proteasomal degradation via the pVHL ubiquitination complex. In this report, we reveal an important function for ARD1 in ... mammalian cells as a protein acetyltransferase by direct binding to HIF-1alpha to regulate its stability. We present further evidence showing that ARD1-mediated acetylation enhances interaction of HIF-1alpha with pVHL and HIF-1alpha ubiquitination, suggesting that the acetylation of HIF-1alpha by ARD1 is critical to proteasomal degradation. Therefore, we have concluded that the role of ARD1 in the acetylation of HIF-1alpha provides a key regulatory mechanism underlying HIF-1alpha stability.
Mesh Terms:
Acetylation, Amino Acid Sequence, Animals, Cell Hypoxia, Cell Line, Cell Line, Transformed, DNA-Binding Proteins, Endoribonucleases, Gene Expression Regulation, Green Fluorescent Proteins, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Luminescent Proteins, Mice, Molecular Sequence Data, Oxygen, Phosphoprotein Phosphatases, Protein Processing, Post-Translational, Protein Structure, Tertiary, RNA-Binding Proteins, Recombinant Proteins, Sequence Deletion, Sequence Homology, Amino Acid, Transcription Factors, Transcriptional Activation, Tumor Cells, Cultured
Acetylation, Amino Acid Sequence, Animals, Cell Hypoxia, Cell Line, Cell Line, Transformed, DNA-Binding Proteins, Endoribonucleases, Gene Expression Regulation, Green Fluorescent Proteins, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Luminescent Proteins, Mice, Molecular Sequence Data, Oxygen, Phosphoprotein Phosphatases, Protein Processing, Post-Translational, Protein Structure, Tertiary, RNA-Binding Proteins, Recombinant Proteins, Sequence Deletion, Sequence Homology, Amino Acid, Transcription Factors, Transcriptional Activation, Tumor Cells, Cultured
Cell
Date: Nov. 27, 2002
PubMed ID: 12464182
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