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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
30
|
| pubmed:dateCreated |
1997-9-9
|
| pubmed:abstractText |
We describe a dominant negative (DN) to activation protein-1 (AP1) that inhibits DNA binding in an equimolar competition. AP1 is a heterodimer of the oncogenes Fos and Jun, members of the bZIP family of transcription factors. The DN, termed A-Fos, consists of a newly designed acidic amphipathic protein sequence appended onto the N-terminus of the Fos leucine zipper, replacing the normal basic region critical for DNA binding. The acidic extension and the Jun basic region form a heterodimeric coiled coil structure that stabilizes the complex over 3000-fold and prevents the basic region of Jun from binding to DNA. Gel shift assays indicate that A-Fos can inactivate the DNA binding of a Fos:Jun heterodimer in an equimolar competition. Transient transfection assays indicate that A-Fos inhibits Jun-dependent transactivation. Both the acidic extension and the Fos leucine zipper are critical for this inhibition. Expression of A-Fos in mouse fibroblasts inhibits focus formation more than colony formation, reflecting the ability of A-Fos to interfere with the AP1 biological functions in mammalian cells. This reagent is more potent than a deletion of either the Fos or Jun transactivation domain, which has been used previously as a dominant negative to AP1 activity.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
25
|
| pubmed:volume |
272
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
18586-94
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:9228025-Amino Acid Sequence,
pubmed-meshheading:9228025-Animals,
pubmed-meshheading:9228025-Binding Sites,
pubmed-meshheading:9228025-Cell Transformation, Neoplastic,
pubmed-meshheading:9228025-DNA,
pubmed-meshheading:9228025-DNA-Binding Proteins,
pubmed-meshheading:9228025-Fluorescent Antibody Technique, Indirect,
pubmed-meshheading:9228025-Humans,
pubmed-meshheading:9228025-Leucine Zippers,
pubmed-meshheading:9228025-Macromolecular Substances,
pubmed-meshheading:9228025-Mice,
pubmed-meshheading:9228025-Models, Molecular,
pubmed-meshheading:9228025-Molecular Sequence Data,
pubmed-meshheading:9228025-Protein Structure, Secondary,
pubmed-meshheading:9228025-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:9228025-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:9228025-Transcription Factor AP-1,
pubmed-meshheading:9228025-Transcriptional Activation,
pubmed-meshheading:9228025-Tumor Cells, Cultured
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
A dominant negative to activation protein-1 (AP1) that abolishes DNA binding and inhibits oncogenesis.
|
| pubmed:affiliation |
Laboratory of Biochemistry, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|