McCurrach, M. E., Connor, T. M., Knudson, C. M., Korsmeyer, S. J., Lowe, S. W.
(March 1997)
bax-deficiency promotes drug resistance and oncogenic transformation by attenuating p53-dependent apoptosis.
Proceedings of the National Academy of Sciences of the United States of America, 94 (6).
pp. 2345-9.
ISSN 0027-8424
Abstract
Inactivation of p53-dependent apoptosis promotes oncogenic transformation, tumor development, and resistance to many cytotoxic anticancer agents. p53 can transcriptionally activate bax, a bcl-2 family member that promotes apoptosis. To determine whether bax is required for p53-dependent apoptosis, the effects of bax deficiency were examined in primary fibroblasts expressing the E1A oncogene, a setting where apoptosis is dependent on endogenous p53. We demonstrate that bax can function as an effector of p53 in chemotherapy-induced apoptosis and contributes to a p53 pathway to suppress oncogenic transformation. Furthermore, we show that additional p53 effectors participate in these processes. These p53-controlled factors act synergistically with Bax to promote a full apoptotic response, and their action is suppressed by the Bcl-2 and E1B 19K oncoproteins. These studies demonstrate that Bax is a determinant of p53-dependent chemosensitivity and illustrate how p53 can promote apoptosis by coordinating the activities of multiple effectors.
| Item Type: |
Paper
|
| Uncontrolled Keywords: |
Animals
Apoptosis
Cell Survival/drug effects
Cell Transformation, Neoplastic
Cells, Cultured
Cisplatin/pharmacology
Crosses, Genetic
Doxorubicin/pharmacology
Drug Resistance/ genetics
Embryo
Etoposide/pharmacology
Fibroblasts
Genes, p53
Mice
Mice, Knockout
Proto-Oncogene Proteins/ deficiency/genetics
Proto-Oncogene Proteins c-bcl-2
RNA, Messenger/biosynthesis
Recombination, Genetic
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Transcription, Genetic
Tumor Suppressor Protein p53/biosynthesis/metabolism
bcl-2-Associated X Protein |
| Subjects: |
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
organism description > animal > developmental stage > embryo
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > tumor suppressor |
| CSHL Authors: |
|
| Communities: |
CSHL labs > Lowe lab |
| Depositing User: |
Kathleen Darby
|
| Date: |
18 March 1997 |
| Date Deposited: |
08 May 2014 14:58 |
| Last Modified: |
11 Sep 2019 16:32 |
| PMCID: |
PMC20090 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/29984 |
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