Linked Life Data

11313879

Source:http://linkedlifedata.com/resource/pubmed/id/11313879

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2001-4-23
pubmed:abstractText
Elk-1, a c-Fos protooncogene regulator, which belongs to the ETS-domain family of transcriptional factors, plays an important role in the induction of immediate early gene expression in response to a variety of extracellular signals. In this study, we demonstrate for the first time the in vitro and in vivo interaction of Elk-1 with BRCA1 splice variants BRCA1a and BRCA1b using GST-pull down assays, co-imunoprecipitations/Western blot analysis of cell extracts from breast cancer cells and mammalian two-hybrid assays. We have localized the BRCA1 interaction domain of Elk-1 protein to the conserved ETS domain, a motif involved in DNA binding and protein-protein interactions. We also observed binding of BRCA1 proteins to other ETS-domain transcription factors SAP1, ETS-1, ERG-2 and Fli-1 but not to Elk-1 splice variant DeltaElk-1 and c-Fos protooncogene. Both BRCA1a and BRCA1b splice variants function as growth suppressors of human breast cancer cells. Interestingly, our studies reveal that although both Elk-1 and SAP-1 are highly homologous members of a subfamily of ETS domain proteins called ternary complex factors, it is only Elk-1 but not SAP-1 that can augment the growth suppressive function of BRCA1a/1b proteins in breast cancer cells. Thus Elk-1 could be a potential downstream target of BRCA1 in its growth control pathway. Furthermore, we have observed inhibition of c-Fos promoter activity in BRCA1a transfected stable breast cancer cells and over expression of BRCA1a/1b attenuates MEK-induced SRE activation in vivo. These results demonstrate for the first time a link between the growth suppressive function of BRCA1a/1b proteins and signal transduction pathway involving Elk-1 protein. All these results taken together suggest that one of the mechanisms by which BRCA1a/1b proteins function as growth/tumor suppressors is through inhibition of the expression of Elk-1 target genes like c-Fos.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1357-67
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11313879-Alternative Splicing, pubmed-meshheading:11313879-Animals, pubmed-meshheading:11313879-BRCA1 Protein, pubmed-meshheading:11313879-Breast Neoplasms, pubmed-meshheading:11313879-DNA-Binding Proteins, pubmed-meshheading:11313879-Female, pubmed-meshheading:11313879-Genes, Tumor Suppressor, pubmed-meshheading:11313879-Genes, fos, pubmed-meshheading:11313879-Humans, pubmed-meshheading:11313879-Mammary Neoplasms, Animal, pubmed-meshheading:11313879-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:11313879-Mitogen-Activated Protein Kinases, pubmed-meshheading:11313879-Nuclear Proteins, pubmed-meshheading:11313879-Protein Binding, pubmed-meshheading:11313879-Proto-Oncogene Proteins, pubmed-meshheading:11313879-Response Elements, pubmed-meshheading:11313879-Serum Response Factor, pubmed-meshheading:11313879-Transcription Factors, pubmed-meshheading:11313879-ets-Domain Protein Elk-1
pubmed:year
2001
pubmed:articleTitle
c-Fos oncogene regulator Elk-1 interacts with BRCA1 splice variants BRCA1a/1b and enhances BRCA1a/1b-mediated growth suppression in breast cancer cells.
pubmed:affiliation
Department of Medicine, Program of Cancer Genetics, Cancer Center, MCP Hahnemann University, 245 North 15th Street, New College Building, M.S. 481, Philadelphia, Pennsylvania 19102, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't