Document Detail


Directed mutation of the basic domain of v-Jun alters DNA binding specificity and abolishes its oncogenic activity in chicken embryo fibroblasts.
MedLine Citation:
PMID:  11039905     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Overexpression of v-Jun in chicken embryo fibroblasts (CEF) leads to oncogenic transformation phenotypically characterized by anchorage independent growth and release from contact inhibition (focus formation). The mechanisms involved in this oncogenic conversion however, are not yet clear. Because Jun is a transcription factor, it has been assumed that oncogenic transformation results directly from deregulated AP-1 target gene expression. However, a number of experimental observations in avian cell culture models fail to correlate oncogenesis with AP-1 activity suggesting that transformation induced by v-Jun may occur through an indirect mechanism. To test this possibility, we introduced point mutations into the basic DNA binding domain of v-Jun and created mutants that exhibit altered binding specificity. When expressed in CEF, these mutants fail to deregulate three known v-Jun target genes (JTAP-1, apolipoprotein A1, c-Jun) thus demonstrating in vivo specificity changes. Each of the binding specificity mutants was also tested for its ability to induce oncogenic transformation. Interestingly, expression of these mutants in CEF results in a phenotype indistinguishable from the vector control with respect to growth rate, focus formation and the ability to form colonies in soft agar. These results are consistent with a model requiring direct AP-1 target deregulation as a prerequisite of v-Jun induced cell transformation. With this in mind, we generated a series of additional mutants that retain the ability to bind AP-1 sequence elements, but vary in their oncogenic potential. We demonstrate the use of these mutants to screen v-Jun induced gene targets for a functional role in cell transformation.
Authors:
J Basso; J Briggs; C Findlay; T Bos
Related Documents :
10805795 - Lexa chimeras reveal the function of drosophila fos as a context-dependent transcriptio...
11698665 - Jac, a direct target of oncogenic transcription factor jun, is involved in cell transfo...
19487245 - Estrogen receptor alpha, fos-related antigen-2, and c-jun coordinately regulate human u...
11835255 - Elliptically polarized magnetic fields do not alter immediate early response genes expr...
25337465 - Improvement in the stability and functionality of nicotiana tabacum produced recombinan...
11496235 - Basophil recruitment and il-4 production during human allergen-induced late asthma.
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  19     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-11-09     Completed Date:  2000-11-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  4876-85     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk 23501, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution*
Animals
Apolipoprotein A-I / biosynthesis,  genetics
Avian Sarcoma Viruses / genetics,  physiology
Cell Transformation, Viral / genetics*
Cells, Cultured
Chick Embryo
DNA / metabolism*
Fibroblasts
Gene Expression Regulation, Viral
Genes, jun*
Models, Biological
Mutagenesis, Site-Directed
Oncogene Protein p65(gag-jun) / chemistry,  genetics*
Point Mutation
Protein Binding
Protein Structure, Tertiary
Proto-Oncogene Proteins c-jun / biosynthesis
Recombinant Fusion Proteins / metabolism
Transcription Factor AP-1 / metabolism
Transfection
Grant Support
ID/Acronym/Agency:
R01 CA 51982/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoprotein A-I; 0/Oncogene Protein p65(gag-jun); 0/Proto-Oncogene Proteins c-jun; 0/Recombinant Fusion Proteins; 0/Transcription Factor AP-1; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  C-erbB-2/ HER-2 upregulates fascin, an actin-bundling protein associated with cell motility, in huma...
Next Document:  B-Myc is preferentially expressed in hormonally-controlled tissues and inhibits cellular proliferati...