Journal ArticleDOI
Thymocyte apoptosis induced by p53-dependent and independent pathways
Alan Richard Clarke,Colin A. Purdie,Colin A. Purdie,David J. Harrison,R. G. Morris,Colin C. Bird,Martin L. Hooper,Andrew H. Wyllie +7 more
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TLDR
The 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.Abstract:
Death by apoptosis is characteristic of cells undergoing deletion during embryonic development, T- and B-cell maturation and endocrine-induced atrophy. Apoptosis can be initiated by various agents 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 Ca(2+)-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.read more
Citations
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Journal ArticleDOI
The mouse lymphoma L5178Y Tk+/− cell line is heterozygous for a codon 170 mutation in the p53 tumor suppressor gene
Richard D. Storer,Andrew R. Kraynak,Troy W. McKelvey,Michael C. Elia,Tamra L. Goodrow,John G. DeLuca +5 more
TL;DR: Results indicate that p53 protein in L5178Y cells is dysfunctional and suggest that this line may therefore be abnormally susceptible to the induction of genetic alterations.
Journal ArticleDOI
Mammalian follicular development and atresia: role of apoptosis.
TL;DR: The role of intraovarian modulators of programmed cell death in the induction of atresia during follicular development is summarized.
Journal ArticleDOI
Ultraviolet B-Radiation Dose Influences the Induction of Apoptosis and p53 in Human Keratinocytes
Jenny Cotton,Dan F. Spandau +1 more
TL;DR: Support is given to increasing evidence that p53 may play a role in both the repair of UV-radiation-induced DNA damage and the induction of apoptosis, and may function as a central control checkpoint in response to UVB-radiated DNA damage.
Book ChapterDOI
The Pharmacology of T Cell Apoptosis
TL;DR: There are two ways for not suffering from hell: accept hell and become part of it to the point that it you will not see it any more and the second way is risky and requires continuous attention and learning.
Journal ArticleDOI
Sp1 and p73 activate PUMA following serum starvation.
TL;DR: The results suggest that transcription factors Sp1 and p73 mediate p53-independent induction of PUMA following serum starvation to trigger apoptosis in human cancer cells.
References
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Journal ArticleDOI
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
TL;DR: It is shown here that this morphological change is closely associated with excision of nucleosome chains from nuclear chromatin, apparently through activation of an intracellular, but non-lysosomal, endonuclease.
Journal ArticleDOI
A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia
Michael B. Kastan,Qimin Zhan,Wafik S. El-Deiry,Tyler Jacks,William V. Walsh,Beverly Plunkett,Bert Vogelstein,Albert J. Fornace +7 more
TL;DR: Three participants are identified (AT gene(s), p53, and GADD45) in a signal transduction pathway that controls cell cycle arrest following DNA damage; abnormalities in this pathway probably contribute to tumor development.
Journal ArticleDOI
Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6
TL;DR: In this article, wild-type p53 protein has many properties consistent with its being the product of a tumour suppressor gene, which could be involved in promoting cell differentiation as well as in mediating growth arrest by growthinhibitory cytokines.
Journal ArticleDOI
Wild-type p53 is a cell cycle checkpoint determinant following irradiation.
TL;DR: Participation of p53 in this pathway suggests a mechanism for the contribution of abnormalities in p53 to tumorigenesis and genetic instability and provides a useful model for studies of the molecular mechanisms of p 53 involvement in controlling the cell cycle.
Journal ArticleDOI
Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis.
TL;DR: The data confirm that the condensed chromatin which characterizes apoptosis morphologically consists of endogenously digested chromatin fragments, and provide support for the view that at least some cells enter apoptosis by a process dependent upon macromolecular synthesis.