Journal article
Role of protein-protein interactions in the antiapoptotic function of EWS-Fli-1
Oncogene, v 23(42), pp 7087-7094
16 Sep 2004
PMID: 15273724
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- Role of protein-protein interactions in the antiapoptotic function of EWS-Fli-1
- Creators
- Ramugounder Ramakrishnan - Drexel UniversityYasuo Fujimura - Morehouse School of MedicineJian Ping Zou - Drexel UniversityFang Liu - Drexel UniversityLeo Lee - Science Applications International CorporationVeena N Rao - Morehouse School of MedicineE Shyam P Reddy - Morehouse School of MedicineLinda Y Lee - College of Engineering (1970-)
- Publication Details
- Oncogene, v 23(42), pp 7087-7094
- Publisher
- Springer Nature
- Grant note
- CA 57322 / NCI NIH HHS R01 CA 85343 / NCI NIH HHS CA 83591 / NCI NIH HHS R01 CA 85642 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Engineering
- Web of Science ID
- WOS:000223885100009
- Scopus ID
- 2-s2.0-4844224145
- Other Identifier
- 991019168668804721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Genetics & Heredity
- Oncology