Document Detail

c-Jun and hypoxia-inducible factor 1 functionally cooperate in hypoxia-induced gene transcription.
MedLine Citation:
PMID:  11739718     Owner:  NLM     Status:  MEDLINE    
Under low-oxygen conditions, cells develop an adaptive program that leads to the induction of several genes, which are transcriptionally regulated by hypoxia-inducible factor 1 (HIF-1). On the other hand, there are other factors which modulate the HIF-1-mediated induction of some genes by binding to cis-acting motifs present in their promoters. Here, we show that c-Jun functionally cooperates with HIF-1 transcriptional activity in different cell types. Interestingly, a dominant-negative mutant of c-Jun which lacks its transactivation domain partially inhibits HIF-1-mediated transcription. This cooperative effect is not due to an increase in the nuclear amount of the HIF-1alpha subunit, nor does it require direct binding of c-Jun to DNA. c-Jun and HIF-1alpha are able to associate in vivo but not in vitro, suggesting that this interaction involves the participation of additional proteins and/or a posttranslational modification of these factors. In this context, hypoxia induces phosphorylation of c-Jun at Ser(63) in endothelial cells. This process is involved in its cooperative effect, since specific blockade of the JNK pathway and mutation of c-Jun at Ser(63) and Ser(73) impair its functional cooperation with HIF-1. The functional interplay between c-Jun and HIF-1 provides a novel insight into the regulation of some genes, such as the one for VEGF, which is a key regulator of tumor angiogenesis.
Arántzazu Alfranca; M Dolores Gutiérrez; Alicia Vara; Julián Aragonés; Felipe Vidal; Manuel O Landázuri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  22     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2001-12-12     Completed Date:  2002-01-15     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12-22     Citation Subset:  IM    
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain.
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MeSH Terms
5' Untranslated Regions / metabolism
Cell Hypoxia*
Cells, Cultured
DNA-Binding Proteins / genetics,  metabolism*
Endothelial Growth Factors / genetics,  metabolism
Endothelium, Vascular / cytology
Gene Expression Regulation / genetics*
Genes, Reporter
Helix-Loop-Helix Motifs
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Lymphokines / genetics,  metabolism
Nuclear Proteins / genetics,  metabolism*
Protein Binding
Proto-Oncogene Proteins c-jun / genetics,  metabolism*
Recombinant Fusion Proteins / metabolism
Transcription Factors*
Transcription, Genetic*
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Reg. No./Substance:
0/5' Untranslated Regions; 0/DNA-Binding Proteins; 0/Endothelial Growth Factors; 0/HIF1A protein, human; 0/Hypoxia-Inducible Factor 1; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Lymphokines; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins c-jun; 0/Recombinant Fusion Proteins; 0/Transcription Factors; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors

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