Abstract |
The p53 tumor suppressor has been implicated in the control of apoptosis in response to various signals, including DNA damage, oncogene activation, and survival factor withdrawal. The p53 protein is a transcription factor capable of sequence-specific transactivation of target genes. The relationship between p53-mediated transactivation and apoptosis was probed in interleukin 3 (IL-3)-dependent DA-1 lymphoma cells. DA-1 cells express endogenous wild-type p53, which is required for the efficient induction of apoptosis by IL-3 deprivation. IL-3 withdrawal caused no detectable increase in p53 and no concomitant activation of p53-responsive promoters. Conversely, high levels of transfected, transcriptionally active p53 did not elicit any apoptosis as long as IL-3 was present; instead, the cells underwent a viable G1 arrest. IL-3 protected DA-1 cells from the apoptotic effect of low doses of radiation. However, higher doses triggered p53-dependent apoptosis, even in the presence of IL-3. Irrespective of their different effects on viability, sublethal and lethal radiation caused a comparable augmentation of p53-dependent transactivation. Lethal radiation induced an initial p53-dependent G1 arrest, but subsequent apoptosis was preceded by cell cycle re-entry. Our data support the conjecture that activities of p53 distinct from specific transcriptional activation may contribute to apoptosis, although activation of genes such as Bax is also likely to play a role.
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Authors | E Gottlieb, S Lindner, M Oren |
Journal | Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
(Cell Growth Differ)
Vol. 7
Issue 3
Pg. 301-10
(Mar 1996)
ISSN: 1044-9523 [Print] United States |
PMID | 8838860
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Bax protein, mouse
- Cdkn1a protein, mouse
- Cyclin-Dependent Kinase Inhibitor p21
- Cyclins
- DNA, Neoplasm
- Interleukin-3
- Proto-Oncogene Proteins
- Proto-Oncogene Proteins c-bcl-2
- RNA, Messenger
- Tumor Suppressor Protein p53
- bcl-2-Associated X Protein
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Topics |
- Animals
- Apoptosis
(physiology, radiation effects)
- Cyclin-Dependent Kinase Inhibitor p21
- Cyclins
(genetics)
- DNA, Neoplasm
(biosynthesis)
- G1 Phase
- Gene Expression
- Interleukin-3
(physiology)
- Lymphocytes
(cytology, physiology)
- Lymphoma
- Mice
- Promoter Regions, Genetic
(physiology)
- Proto-Oncogene Proteins
(genetics)
- Proto-Oncogene Proteins c-bcl-2
- RNA, Messenger
(biosynthesis)
- Radiation, Ionizing
- Transcriptional Activation
(physiology)
- Tumor Cells, Cultured
- Tumor Suppressor Protein p53
(biosynthesis, physiology)
- bcl-2-Associated X Protein
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