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Role of protein-protein interactions in the antiapoptotic function of EWS-Fli-1
Journal article   Peer reviewed

Role of protein-protein interactions in the antiapoptotic function of EWS-Fli-1

Ramugounder Ramakrishnan, Yasuo Fujimura, Jian Ping Zou, Fang Liu, Leo Lee, Veena N Rao, E Shyam P Reddy and Linda Y Lee
Oncogene, v 23(42), pp 7087-7094
16 Sep 2004
PMID: 15273724

Abstract

Actins - genetics Apoptosis - physiology Base Sequence Bone Neoplasms - genetics Cell Survival - physiology Chromosomes, Human, Pair 11 - genetics Chromosomes, Human, Pair 22 - genetics DNA Primers Gelsolin - genetics Gelsolin - pharmacology Humans Microfilament Proteins Polymerase Chain Reaction - methods Receptors, Cytoplasmic and Nuclear - genetics Sarcoma, Ewing - genetics Transcription, Genetic Transfection Translocation, Genetic
In the majority of Ewing's family tumors, chromosomal translocation t(11;22) leads to aberrant fusion of RNA-binding protein EWS with DNA-binding ETS transcriptional factor Fli-1. EWS-Fli-1 has altered the transcriptional activity and modulating its downstream target genes through this transcriptional activity is thought to be responsible for this tumor. We have previously shown that both EWS-Fli-1 and Fli-1 have antiapoptotic activity against several apoptotic inducers. Here, we show that the transcriptional activity of EWS-Fli-1 and Fli-1 is not essential for its antiapoptotic activity. We also demonstrate that EWS-Fli-1 and Fli-1 interact with CBP through its amino-terminal region and inhibit the CBP-dependent transcriptional activity of RXR. This activity appears to be independent of DNA-binding activity of EWS-Fli-1. Introduction of the dominant-negative form of CBP into Ewing's sarcoma cells sensitizes these cells against genotoxic or retinoic-acid induced apoptosis. These results suggest that the ability of EWS-Fli-1/Fli-1 to target transcriptional cofactor(s) and modulate apoptotic pathways may be responsible for its antiapoptotic and tumorigenic activities.

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Collaboration types
Industry collaboration
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Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
Genetics & Heredity
Oncology
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