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.
Pubmed ID: 12464182 RIS Download
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