Source:http://linkedlifedata.com/resource/pubmed/id/18791271
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
2008-9-15
|
| pubmed:abstractText |
Hypoxia is a hallmark of solid cancers and triggers the transcription of genes responsible for cell survival. The transcription factor Hypoxia-Inducible Factor 1 (HIF-1) is a key regulator in this response and frequently activated in human cancer. HIF-1 activation is associated with tumor aggressiveness and poor clinical outcome and, therefore, may provide an attractive therapeutic target. Here we provide a novel approach for HIF-1 targeted therapy using single-domain llama antibodies directed against the HIF-1alpha oxygen dependent degradation domain which encompass the N-terminal transactivation domain. Conditional expression of HIF intrabodies in mammalian cells interfered with binding to pVHL and inhibited hypoxia induced activation of endogenous target genes. Inducible intrabody targeting is a highly specific strategy for temporal protein inactivation and may have applications for disease treatment.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:issn |
1570-5870
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
30
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
397-409
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:18791271-Animals,
pubmed-meshheading:18791271-Antibody Affinity,
pubmed-meshheading:18791271-Antibody Specificity,
pubmed-meshheading:18791271-Blotting, Western,
pubmed-meshheading:18791271-Camelids, New World,
pubmed-meshheading:18791271-Cell Line, Tumor,
pubmed-meshheading:18791271-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:18791271-Fluorescent Antibody Technique,
pubmed-meshheading:18791271-Humans,
pubmed-meshheading:18791271-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:18791271-Immunoglobulin Fragments,
pubmed-meshheading:18791271-Immunoprecipitation,
pubmed-meshheading:18791271-Promoter Regions, Genetic,
pubmed-meshheading:18791271-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:18791271-Transcription, Genetic,
pubmed-meshheading:18791271-Transfection
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
Conditional inactivation of HIF-1 using intrabodies.
|
| pubmed:affiliation |
Department of Pathology, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|