Bcl-2 is an apoptotic target suppressed by both c-Myc and E2F-1
Eischen, Christine M., Packham, Graham, Nip, John, Fee, Brian E., Hiebert, Scott W., Zambetti, Gerard P. and Cleveland, John L. (2001) Bcl-2 is an apoptotic target suppressed by both c-Myc and E2F-1. Oncogene, 20, (48), 6983-6993.
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Description/Abstract
Malignant transformation occurs in cells that overexpress c-Myc or that inappropriately activate E2F-1. Transformation occurs after the selection of cells that have acquired resistance to apoptosis that is triggered by these oncogenes, and a key mediator of this cell death process is the p53 tumor suppressor. In IL-3-dependent immortal 32D.3 myeloid cells the ARF/p53 apoptotic pathway is inactivated, as these cells fail to express ARF. Nonetheless, both c-Myc and E2F-1 overexpression accelerated apoptosis when these cells were deprived of IL-3. Here we report that c-Myc or E2F-1 overexpression suppresses Bcl-2 protein and RNA levels, and that restoration of Bcl-2 protein effectively blocks the accelerated apoptosis that occurs when c-Myc- or E2F-1-overexpressing cells are deprived of IL-3. Blocking p53 activity with mutant p53 did not abrogate E2F-1-induced suppression of Bcl-2. Analysis of immortal myeloid cells engineered to overexpress c-Myc and E2F-1 DNA binding mutants revealed that DNA binding activity of these oncoproteins is required to suppress Bcl-2 expression. These results suggest that the targeting of Bcl-2 family members is an important mechanism of oncogene-induced apoptosis, and that this occurs independent of the ARF/p53 pathway.
| Item Type: | Article |
|---|---|
| Related URLs: | |
| Keywords: | c-myc, e2f-1, bcl-2, bcl-xl, myeloid, apoptosis |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) Q Science > QH Natural history > QH426 Genetics |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Cancer Sciences |
| Item ID: | 26289 |
| Date Deposited: | 24 Apr 2006 |
| Last Modified: | 01 Apr 2012 02:33 |
| Contributors: | Eischen, Christine M. (Author) Packham, Graham (Author) Nip, John (Author) Fee, Brian E. (Author) Hiebert, Scott W. (Author) Zambetti, Gerard P. (Author) Cleveland, John L. (Author) |
| Date: | 2001 |
| Status: | Published |
| Contact Email Address: | john.cleveland@stjude.org |
| URI: | http://eprints.soton.ac.uk/id/eprint/26289 |
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