title: Binding and regulation of HIF-1alpha by a subunit of the proteasome complex, PSMA7.
abstract: The hypoxia-inducible factor-1alpha (HIF-1alpha) is an important transcription factor for cellular responses to oxygen tension. It is rapidly degraded under normoxic conditions by the ubiquitin-dependent proteasome pathway. Here we report a critical role of the 20S proteasome subunit PSMA7 in HIF-1alpha regulation. PSMA7 was found to interact specifically with two subdomains of HIF-1alpha. PSMA7 inhibited the transactivation function of HIF-1alpha under both normoxic and hypoxia-mimicking conditions. In addition, we show that the PSMA7-mediated regulation of HIF-1alpha activity is associated with the proteasome pathway.
authors.affiliation: Center for Cellular Switch Protein Structure, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon, South Korea. scho@mail.kribb.re.kr
authors.forename: S
authors.initials: S
authors.lastname: Cho
authors.forename: Y J
authors.initials: YJ
authors.lastname: Choi
authors.forename: J M
authors.initials: JM
authors.lastname: Kim
authors.forename: S T
authors.initials: ST
authors.lastname: Jeong
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: S E
authors.initials: SE
authors.lastname: Ryu
mesh_terms: D001665:Binding Sites; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009097:Multienzyme Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D017434:Protein Structure, Tertiary; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D014157:Transcription Factors; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex