Linked Life Data

14534527

Source:http://linkedlifedata.com/resource/pubmed/id/14534527

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
44
pubmed:dateCreated
2003-10-9
pubmed:abstractText
In Ewing's sarcoma family tumors, the ets transcription factor gene FLI1 is rearranged with one EWS allele resulting in coexpression of germline EWS and chimeric EWS-FLI1 proteins. Here, we investigated the potential of germline EWS, FLI1 and EWS-FLI1 to oligomerize. In two functional in vivo tests, fluorescence resonance energy transfer (FRET) and the mammalian two-hybrid (MTH) assay, self-association of EWS and EWS-FLI1, but not of FLI1 was detected. In addition, interaction of EWS-FLI1 with EWS and FLI1 was observed. GST pull-down assays and immunoprecipitation experiments largely confirmed these results. The EWS N-terminal domain present in both EWS and EWS-FLI1 was found to contribute to homotypic and heterotypic interactions of these proteins. However, in the context of germline EWS, the presence of the whole or part of the C-terminal RNA-binding domain greatly supported the self-association potential of the protein. Involvement of an RNA component in EWS oligomerization was confirmed by sensitivity of the corresponding GST pull-down assay to RNaseA treatment. In contrast, EWS-FLI1 was able to self-associate and also bind to FLI1 via its C-terminal domain, which comprises the FLI1 DNA-binding motif. Accordingly, the EWS-FLI1 interaction was not disrupted by RNaseA treatment. Despite its potential to oligomerize, EWS-FLI1 bound to a tandem ets-binding site of the TGFbeta type II receptor promoter as a monomer. Therefore, the functional consequences of homo- and hetero-oligomerization of EWS and EWS-FLI1 proteins remain to be elucidated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6819-29
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:14534527-Amino Acid Sequence, pubmed-meshheading:14534527-Artificial Gene Fusion, pubmed-meshheading:14534527-DNA-Binding Proteins, pubmed-meshheading:14534527-Dimerization, pubmed-meshheading:14534527-Gene Expression Regulation, Neoplastic, pubmed-meshheading:14534527-HeLa Cells, pubmed-meshheading:14534527-Humans, pubmed-meshheading:14534527-Oncogene Proteins, Fusion, pubmed-meshheading:14534527-Protein Structure, Tertiary, pubmed-meshheading:14534527-Proto-Oncogene Protein c-fli-1, pubmed-meshheading:14534527-Proto-Oncogene Proteins, pubmed-meshheading:14534527-RNA-Binding Protein EWS, pubmed-meshheading:14534527-Sarcoma, Ewing, pubmed-meshheading:14534527-Sequence Deletion, pubmed-meshheading:14534527-Trans-Activators, pubmed-meshheading:14534527-Transcription Factors, pubmed-meshheading:14534527-Tumor Cells, Cultured
pubmed:year
2003
pubmed:articleTitle
Homotypic and heterotypic interactions of EWS, FLI1 and their oncogenic fusion protein.
pubmed:affiliation
Children's Cancer Research Institute, St Anna Kinderspital, A-1090 Vienna, Austria.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't