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

Bcl-2 is an apoptotic target suppressed by both c-Myc and E2F-1
Bcl-2 is an apoptotic target suppressed by both c-Myc and E2F-1
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.
c-myc, e2f-1, bcl-2, bcl-xl, myeloid, apoptosis
0950-9232
6983-6993
Eischen, Christine M.
3b84e0e0-82b3-4264-80ae-43ec1f782f10
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Nip, John
6d2042a8-edfb-44d5-b4bf-0290157d10ac
Fee, Brian E.
9b46a669-b1ed-4d60-88cd-702ee57e06b3
Hiebert, Scott W.
c9251693-6803-44be-ac2b-81ffb27e8e97
Zambetti, Gerard P.
fea339d1-e8f0-4f78-abae-0e12ab38ed4e
Cleveland, John L.
b24e373b-6b1e-45c4-a808-9ee2ebb00d37
Eischen, Christine M.
3b84e0e0-82b3-4264-80ae-43ec1f782f10
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Nip, John
6d2042a8-edfb-44d5-b4bf-0290157d10ac
Fee, Brian E.
9b46a669-b1ed-4d60-88cd-702ee57e06b3
Hiebert, Scott W.
c9251693-6803-44be-ac2b-81ffb27e8e97
Zambetti, Gerard P.
fea339d1-e8f0-4f78-abae-0e12ab38ed4e
Cleveland, John L.
b24e373b-6b1e-45c4-a808-9ee2ebb00d37

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.

Record type: Article

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.

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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
ORCID for Graham Packham: ORCID iD orcid.org/0000-0002-9232-5691

Catalogue record

Date deposited: 24 Apr 2006
Last modified: 23 Jul 2022 01:46

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Contributors

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

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