Linked Life Data

9287359

Source:http://linkedlifedata.com/resource/pubmed/id/9287359

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
1997-10-1
pubmed:abstractText
Hypoxia is a pathophysiological condition that occurs during injury, ischemia, and stroke. It is characterized by a decrease of reactive oxygen intermediates and a change of the intracellular redox level. In tumors hypoxia is regarded as a trigger for enhanced growth and metastasis. Here we report that in HeLa cells, hypoxic conditions induce the transcriptional activation of c-fos transcription via the serum response element. Mutations in the binding site for the ternary complex factor Elk-1 and the serum response factor abolished this induction, indicating that a ternary complex at the serum response element is necessary for the induction of the c-fos gene under hypoxia. The transcription factor Elk-1 was covalently modified by phosphorylation in response to hypoxia. Furthermore this hyperphosphorylation of Elk-1, the activation of mitogen-activated protein kinase (MAPK), and the induction of c-fos transcripts were blocked by PD98059, a specific inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase kinase 1. An in vitro kinase assay with Elk-1 as substrate showed that MAPK is activated under hypoxia. The activation of MAPK corresponds temporally with the phosphorylation and activation of Elk-1. Thus, a decrease of the intracellular reactive oxygen intermediate level by hypoxia induces c-fos via the MAPK pathway. These results suggest that the intracellular redox levels may be directly coupled to tumor growth, invasion, and metastasis via Elk-1-dependent induction of c-Fos controlled genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23435-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9287359-Anaerobiosis, pubmed-meshheading:9287359-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:9287359-DNA-Binding Proteins, pubmed-meshheading:9287359-Enzyme Activation, pubmed-meshheading:9287359-Gene Expression Regulation, pubmed-meshheading:9287359-HeLa Cells, pubmed-meshheading:9287359-Humans, pubmed-meshheading:9287359-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:9287359-Oxidation-Reduction, pubmed-meshheading:9287359-Oxygen, pubmed-meshheading:9287359-Phosphorylation, pubmed-meshheading:9287359-Promoter Regions, Genetic, pubmed-meshheading:9287359-Protein Binding, pubmed-meshheading:9287359-Proto-Oncogene Proteins, pubmed-meshheading:9287359-Proto-Oncogene Proteins c-fos, pubmed-meshheading:9287359-Signal Transduction, pubmed-meshheading:9287359-Transcription, Genetic, pubmed-meshheading:9287359-Transcription Factors, pubmed-meshheading:9287359-ets-Domain Protein Elk-1
pubmed:year
1997
pubmed:articleTitle
Hypoxia induces c-fos transcription via a mitogen-activated protein kinase-dependent pathway.
pubmed:affiliation
Institute of Biochemistry and Molecular Biology, Albert-Ludwigs-Universität Freiburg, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't