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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
32
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pubmed:dateCreated |
2007-8-6
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pubmed:abstractText |
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that functions as a master regulator of oxygen homeostasis. The HIF-1alpha subunit is subjected to O(2)-dependent prolyl hydroxylation leading to ubiquitination by the von Hippel-Lindau protein (VHL)-Elongin C ubiquitin-ligase complex and degradation by the 26 S proteasome. In this study, we demonstrate that spermidine/spermine-N(1)-acetyltransferase (SSAT) 2 plays an essential role in this process. SSAT2 binds to HIF-1alpha, VHL, and Elongin C and promotes ubiquitination of hydroxylated HIF-1alpha by stabilizing the interaction of VHL and Elongin C. Multivalent interactions by SSAT2 provide a mechanism to ensure efficient complex formation, which is necessary for the extremely rapid ubiquitination and degradation of HIF-1alpha that is observed in oxygenated cells.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP dependent 26S protease,
http://linkedlifedata.com/resource/pubmed/chemical/Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/VHL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Von Hippel-Lindau Tumor Suppressor...,
http://linkedlifedata.com/resource/pubmed/chemical/diamine N-acetyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/elongin
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
23572-80
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17558023-Acetyltransferases,
pubmed-meshheading:17558023-Anoxia,
pubmed-meshheading:17558023-Cell Line,
pubmed-meshheading:17558023-Genetic Vectors,
pubmed-meshheading:17558023-Glutathione Transferase,
pubmed-meshheading:17558023-Humans,
pubmed-meshheading:17558023-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:17558023-Models, Biological,
pubmed-meshheading:17558023-Oxygen,
pubmed-meshheading:17558023-Proteasome Endopeptidase Complex,
pubmed-meshheading:17558023-Protein Binding,
pubmed-meshheading:17558023-Transcription Factors,
pubmed-meshheading:17558023-Two-Hybrid System Techniques,
pubmed-meshheading:17558023-Ubiquitin-Protein Ligases,
pubmed-meshheading:17558023-Von Hippel-Lindau Tumor Suppressor Protein
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pubmed:year |
2007
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pubmed:articleTitle |
Spermidine/spermine-N1-acetyltransferase 2 is an essential component of the ubiquitin ligase complex that regulates hypoxia-inducible factor 1alpha.
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pubmed:affiliation |
Vascular Biology Program, Institute for Cell Engineering, Department of Pediatrics, and McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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