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rdf:type |
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lifeskim:mentions |
umls-concept:C0085862,
umls-concept:C0243044,
umls-concept:C0243125,
umls-concept:C0699900,
umls-concept:C0719453,
umls-concept:C0965644,
umls-concept:C1167622,
umls-concept:C1299583,
umls-concept:C1333897,
umls-concept:C1415151,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1549571,
umls-concept:C1556066,
umls-concept:C1608386,
umls-concept:C1619636,
umls-concept:C1704838,
umls-concept:C1825534
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pubmed:issue |
2
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pubmed:dateCreated |
2007-1-24
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pubmed:abstractText |
Hypoxia-inducible factor 1 (HIF-1) regulates transcription in response to changes in O(2) concentration. O(2)-dependent degradation of the HIF-1alpha subunit is mediated by prolyl hydroxylase (PHD), the von Hippel-Lindau (VHL)/Elongin-C/Elongin-B E3 ubiquitin ligase complex, and the proteasome. Inhibition of heat-shock protein 90 (HSP90) leads to O(2)/PHD/VHL-independent degradation of HIF-1alpha. We have identified the receptor of activated protein kinase C (RACK1) as a HIF-1alpha-interacting protein that promotes PHD/VHL-independent proteasomal degradation of HIF-1alpha. RACK1 competes with HSP90 for binding to the PAS-A domain of HIF-1alpha in vitro and in human cells. HIF-1alpha degradation induced by the HSP90 inhibitor 17-allylaminogeldanamycin is abolished by RACK1 loss of function. RACK1 binds to Elongin-C and promotes ubiquitination of HIF-1alpha. Elongin-C-binding sites in RACK1 and VHL show significant sequence similarity. Thus, RACK1 is an essential component of an O(2)/PHD/VHL-independent mechanism for regulating HIF-1alpha stability through competition with HSP90 and recruitment of the Elongin-C/B ubiquitin ligase complex.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-10205047,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-10217175,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-10353251,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-10944113,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-11139474,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-11292861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-11292862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-11504942,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-11516626,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-11595184,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-11598268,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-11641274,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-11689469,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-11980636,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-12004076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-12048197,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-12052835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-12080085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-12435793,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-12912907,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-14508491,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-14624223,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-14645546,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-14764593,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-15140893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-15374877,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-15467455,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-16046841,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-16061178,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-16175177,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-16565084,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-16735998,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-16842157,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-7539918,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-8302854,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17244529-9653127
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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/17-(allylamino)-17-demethoxygeldanam...,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/GNB2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/HSP90 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
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/elongin
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1097-2765
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pubmed:author |
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