title: Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation.
abstract: 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.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 151-742, Seoul, South Korea.
authors.forename: Joo Won
authors.initials: JW
authors.lastname: Jeong
authors.forename: Moon Kyoung
authors.initials: MK
authors.lastname: Bae
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Ahn
authors.forename: Se Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Tae Kwon
authors.initials: TK
authors.lastname: Sohn
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Bae
authors.forename: Mi Ae
authors.initials: MA
authors.lastname: Yoo
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Song
authors.forename: Kong Joo
authors.initials: KJ
authors.lastname: Lee
authors.forename: Kyu Won
authors.initials: KW
authors.lastname: Kim
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004722:Endoribonucleases / Q000378:metabolism*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism; D010749:Phosphoprotein Phosphatases; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008164:Luminescent Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D004722:Endoribonucleases; D010749:Phosphoprotein Phosphatases; C097081:PPP1R8 protein, human; D010100:Oxygen