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Thymocyte Apoptosis Induced By P53-dependent And Independent Pathways
A. Clarke, C. Purdie, D. Harrison, R. G. Morris, C. Bird, M. Hooper, A. Wyllie
Published 1993 · Biology, Medicine
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DEATH by apoptosis is characteristic of cells undergoing deletion during embryonic development, T- and B-cell maturation and endocrine-induced atrophy1. Apoptosis can be initiated by various agents1–5 and may be a result of expression of the oncosuppressor gene p53 (refs 6–8). Here we study the dependence of apoptosis on p53 expression in cells from the thymus cortex. Short-term thymocyte cultures were prepared from mice constitutively heterozygous or homozygous for a deletion in the p53 gene introduced into the germ line after gene targeting. Wild-type thymocytes readily undergo apoptosis after treatment with ionizing radiation, the glucocorticoid methylprednisolone, or etoposide (an inhibitor of topoisomerase II), or after Ca2+-dependent activation by phorbol ester and a calcium ionophore. In contrast, homozygous null p53 thymocytes are resistant to induction of apoptosis by radiation or etoposide, but retain normal sensitivity to glucocorticoid and calcium. The time-dependent apoptosis that occurs in untreated cultures is unaffected by p53 status. Cells heterozygous for p53 deletion are partially resistant to radiation and etoposide. Our results show that p53 exerts a significant and dose-dependent effect in the initiation of apoptosis, but only when it is induced by agents that cause DNA-strand breakage.
This paper references
Monoclonal antibody analysis of p53 expression in normal and transformed cells.
J. Yewdell (1986)
Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures
C. A. Smith (1989)
Cooperative interaction between c-myc and bcl-2 proto-oncogenes
A. Fanidi (1992)
A pgk::hprt fusion as a selectable marker for targeting of genes in mouse embryonic stem cells: disruption of the T-cell receptor delta-chain-encoding gene.
N. V. D. van der Lugt (1991)
Antiproliferative activity of a pregnancy recognition hormone, ovine trophoblast protein-1.
C. Pontzer (1991)
Cloning of the active thymidine kinase gene of herpes simplex virus type 1 in Escherichia coli K-12.
F. Colbère-Garapin (1979)
Analysis of the gene coding for the murine cellular tumour antigen p53.
B. Bienz (1984)
Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6
E. Yonish-Rouach (1991)
The topoisomerase II inhibitor teniposide (VM-26) induces apoptosis in unstimulated mature murine lymphocytes.
C. Roy (1992)
Cell cycle analysis of p53-induced cell death in murine erythroleukemia cells.
J. J. Ryan (1993)
Topoisomerase II-reactive chemotherapeutic drugs induce apoptosis in thymocytes.
P. Walker (1991)
Gene induction by gamma-irradiation leads to DNA fragmentation in lymphocytes.
K. Sellins (1987)
Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line.
P. Shaw (1992)
The mouse Pgk-1 gene promoter contains an upstream activator sequence.
M. McBurney (1991)
Chromatin cleavage in apoptosis: Association with condensed chromatin morphology and dependence on macromolecular synthesis
A. Wyllie (1984)
Effect of gamma-irradiation on DNA-dependent RNA polymerase activity in rat thymus cells.
B. D. Zhivotovsky (1982)
HPRT-deficient (Lesch–Nyhan) mouse embryos derived from germline colonization by cultured cells
M. Hooper (1987)
A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia
M. Kastan (1992)
Regulation of T lymphocyte apoptosis. Signals for the antagonism between activation- and glucocorticoid-induced death.
R. Iseki (1991)
Cellular signalling in programmed cell death (apoptosis).
D. McConkey (1990)
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
A. Wyllie (1980)
Differential induction of secondary DNA fragmentation by topoisomerase II inhibitors in human tumor cell lines with amplified c-myc expression.
R. Bertrand (1991)
Requirement for a functional Rb-1 gene in murine development
A. Clarke (1992)
Analysis of a bacterial hygromycin B resistance gene by transcriptional and translational fusions and by DNA sequencing.
K. R. Kaster (1983)
Apoptosis: mechanisms and roles in pathology.
M. Arends (1991)
Wild-type p53 is a cell cycle checkpoint determinant following irradiation.
S. Kuerbitz (1992)
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Cell Survival following DNA Damage-associated G 1 Checkpoint Does Not Decrease p 53 Loss of a Updated Version
William J. Slichenmyer (2006)
Studies on the immortalisation of rodent embryo fibroblasts by simian virus 40 large tumour antigen.
Powell Aj (1995)
Turning p53 on or off: either way may treat cancer.
D. Fisher (2000)
3-Methylcholanthrene triggers the differentiation of alveolar tumor cells from canine bronchial basal cells and an altered p53 gene promotes their clonal expansion
A. TenHave-Opbroek (2000)
Mismatch repair and p53 independently affect sensitivity to N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea.
G. Aquilina (2000)
The effects of p53 status and human papillomavirus infection on the clinical outcome of patients with Stage IIIB cervical carcinoma treated with radiation therapy alone
H. Ishikawa (2001)
Mdm-2 and ubiquitin-independent p53 proteasomal degradation regulated by NQO1
G. Asher (2002)
p53 functional assays: detecting p53 mutations in both the germline and in sporadic tumours
R. Camplejohn (2001)
E1A oncogene-induced cellular sensitization to immune-mediated apoptosis is independent of p53 and resistant to blockade by E1B 19 kDa protein.
J. Cook (1999)
Enhanced radiosensitivity of malignant glioma cells after adenoviral p53 transduction.
W. Broaddus (1999)
The c-fos Proto-Oncogene Is a Target for Transactivation by the p53 Tumor Suppressor
A. Elkeles (1999)
Normal p53 Function in Primary Cells Deficient for Siah Genes
I. Frew (2002)
Deficiency of clusterin inhibits neointimal hyperplasia after vascular injury.
T. Shirasawa (2009)
Sequence-specific poisons of type II DNA topoisomerases
G. Capranico (1998)
The shape of cell death.
M. Leist (1997)
Distinct target genes and effector processes appear to be critical for p53-activated responses to acute DNA damage versus p53-mediated tumour suppression
L. J. Valente (2013)
Growth and Differentiation COOH-terminal Site Exert Divergent Effects on Thyroid Cell Genes Mutated in the DNA Binding Site or at a Specific p 53 Updated
A. Casamassimi (2006)
Cell‐free reconstitution of Fas‐, UV radiation‐ and ceramide‐induced apoptosis.
S. J. Martin (1995)
Multifaceted roles of nitric oxide in the lateral geniculate nucleus: from visual signal transduction to neuronal apoptosis.
C. Nucci (2003)
Mechanisms of glucocorticoid-mediated apoptosis in hematological malignancies.
S. Greenstein (2002)
Ionizing radiation and epothilone - Mechanism and efficacy in combined radiochemotherapy
B. Hofstetter (2005)
Pyrimidine nucleoside analogs in cancer treatment
C. Galmarini (2003)
Intrasteric regulation of MDM2.
Harumi Shimizu (2003)
Mitogen-Activated Protein Kinase Phosphatase 2 : A Novel Transcription Target of p 53 in Apoptosis
W. Shen (2006)
Retention of wild‐type p53 in tumors from p53 heterozygous mice: reduction of p53 dosage can promote cancer formation
S. Venkatachalam (1998)
Genetic Interactions between the Wilms ’ Tumor 1 Gene and the p 53 Gene 1
A. Menke (2002)
Integral role of Noxa in p53-mediated apoptotic response.
Tsukasa Shibue (2003)
Apoptosis is inversely related to necrosis and determines net growth in tumors bearing constitutively expressed myc, ras, and HPV oncogenes.
M. Arends (1994)
DNA Double-Strand Breaks , p 53 , and Apoptosis during Lymphomagenesis in seid / seid Mice
K. Gurley (2006)
Active Cell Death and Cancer
W. Bursch (1995)
Radiation‐induced cutaneous carcinoma of the head and neck: is there an early role for p53 mutations?
A. Franchi (2006)
Upregulation of the Elongation Factor-1α Gene by p53 in Association With Death of an Erythroleukemic Cell Line
M. Kato (1997)See more