Binding and regulation of HIF-1alpha by a subunit of the proteasome complex, PSMA7.
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.
Cho
S
S
Center for Cellular Switch Protein Structure, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon, South Korea. scho@mail.kribb.re.kr
Choi
Y J
YJ
Kim
J M
JM
Jeong
S T
ST
Kim
J H
JH
Kim
S H
SH
Ryu
S E
SE
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
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