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
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p53-dependent apoptosis or growth arrest induced by different forms of radiation in U2OS cells: p21WAF1/CIP1 repression in UV induced apoptosis.
Lindsey A. Allan,Mike Fried +1 more
TL;DR: It is found that the osteosarcoma cell line, U2OS, is capable of undergoing either p53 dependent apoptosis or cell cycle arrest in response to distinct forms of radiation and that the repression of p21WAF1/CIP1 after UVC may contribute to the efficient induction of apoptosis in Response to this particular insult.
Journal ArticleDOI
Nodal CT density and total tumor volume as prognostic factors after radiation therapy of stage III/IV head and neck cancer
Gerhard G. Grabenbauer,H. Steininger,Martin Meyer,Rainer Fietkau,Thomas Brunner,Pia Heinkelmann,Joachim Hornung,H. Iro,W. Spitzer,Luitpold Distel,Thomas Kirchner,Rolf Sauer +11 more
TL;DR: Nodal CT density, total tumor volume and age will remain the relevant prognostic factors in stage III/IV head and neck cancer.
Journal ArticleDOI
PUMA promotes Bax translocation by both directly interacting with Bax and by competitive binding to Bcl-X L during UV-induced apoptosis.
Yingjie Zhang,Da Xing,Lei Liu +2 more
TL;DR: This study investigated the tripartite nexus among PUMA, Bax, and Bcl-X(L) in living human lung adenocarcinoma cells (ASTC-a-1) to illustrate how PUMA promotes Bax translocation to initiate apoptosis and created an important conclusion that PUma promotes BAX translocation by both by directly interacting with Bax and by competitive binding to B Cl-X-L in UV-induced apoptosis.
Journal ArticleDOI
Apoptosis and cell division.
Journal ArticleDOI
The novel trinuclear platinum complex BBR3464 induces a cellular response different from cisplatin.
Tiziana Servidei,Cristiano Ferlini,Anna Riccardi,Daniela Meco,Giovanni Scambia,Giuseppe Segni,C. Manzotti,Riccardo Riccardi +7 more
TL;DR: The data indicate that BBR3464 may be a promising agent in the treatment of tumours unresponsive to cisplatin and with a non-functional p53, supporting the view that the two drugs act through different mechanisms.
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.
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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.
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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.
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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.