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Bcl-2 is an apoptotic target suppressed by both c-Myc and E2F-1

Record type: Article

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.

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Citation

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), pp. 6983-6993.

More information

Published date: 2001
Keywords: c-myc, e2f-1, bcl-2, bcl-xl, myeloid, apoptosis

Identifiers

Local EPrints ID: 26289
URI: http://eprints.soton.ac.uk/id/eprint/26289
ISSN: 0950-9232
PURE UUID: 8e14a3f6-fdcf-4329-ab8b-3edaa353e05f

Catalogue record

Date deposited: 24 Apr 2006
Last modified: 17 Jul 2017 16:07

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Contributors

Author: Christine M. Eischen
Author: Graham Packham
Author: John Nip
Author: Brian E. Fee
Author: Scott W. Hiebert
Author: Gerard P. Zambetti
Author: John L. Cleveland

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