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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
46
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pubmed:dateCreated |
2001-11-15
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pubmed:abstractText |
The recurrent t(12;22) (q13;q12) chromosomal translocation associated with soft tissue clear cell sarcoma results in a chimeric protein EWS-ATF-1 that acts as a constitutive transcriptional activator. The CBP/p300 transcriptional coactivator, which links various transcriptional factors to basal transcription apparatus, participates in transcriptional activation, growth and cell cycle control and differentiation. In this study, we show that EWS-ATF-1 associates constitutively with CBP both in vitro and in vivo. Both EWS and ATF-1 fusion domains are needed for this interaction. Here, we demonstrate that EWS-ATF-1 represses p53/CBP-mediated trans-activation function. Overexpression of CBP can counteract this repressive effect of EWS-ATF-1. Taken together, these findings suggest that one of the mechanisms by which EWS-ATF-1 may cause tumors is through targeting CBP/p300 resulting in the loss of function of p53. This novel mechanism may be responsible for the development of these and other related solid tumors.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6653-9
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11709699-Blotting, Western,
pubmed-meshheading:11709699-Dose-Response Relationship, Drug,
pubmed-meshheading:11709699-Genes, p53,
pubmed-meshheading:11709699-Glutathione Transferase,
pubmed-meshheading:11709699-Humans,
pubmed-meshheading:11709699-Models, Genetic,
pubmed-meshheading:11709699-Nuclear Proteins,
pubmed-meshheading:11709699-Oncogene Proteins, Fusion,
pubmed-meshheading:11709699-Plasmids,
pubmed-meshheading:11709699-Precipitin Tests,
pubmed-meshheading:11709699-Protein Binding,
pubmed-meshheading:11709699-Protein Structure, Tertiary,
pubmed-meshheading:11709699-Sarcoma, Clear Cell,
pubmed-meshheading:11709699-Soft Tissue Neoplasms,
pubmed-meshheading:11709699-Trans-Activators,
pubmed-meshheading:11709699-Transcription, Genetic,
pubmed-meshheading:11709699-Transcription Factors,
pubmed-meshheading:11709699-Transcriptional Activation,
pubmed-meshheading:11709699-Transfection,
pubmed-meshheading:11709699-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
EWS-ATF-1 chimeric protein in soft tissue clear cell sarcoma associates with CREB-binding protein and interferes with p53-mediated trans-activation function.
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pubmed:affiliation |
Program of Cancer Genetics, Department of Biochemistry, School of Medicine, MCP Hahnemann University, Broad and Vine, Philadelphia, PA 19102, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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