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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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.
|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
|Date Deposited:||24 Apr 2006|
|Last Modified:||27 Mar 2014 18:15|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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