Modulations of glucocorticoid-induced apoptosis linked to the p53 deletion and to the apoptosis susceptibility gene Rapop1 (Radiation-induced apoptosis 1)

Mori, Nobuko; Yamate, Jyoji; Stassen, Alphons P. M.; Oka, Syuntaro; Okumoto, Masaaki; Tsubura, Airo; Akamatsu, Takako; Sakuma, Shinya; Démant, Peter

doi:10.1038/sj.onc.1202719

Cited by 10 publications

(5 citation statements)

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“…Genotypes for the wild-type and targeted alleles of p53 and Atm genes were determined by analyzing the PCR products for these alleles. Amplification for the p53 alleles was done as described elsewhere [27]. The wild-type and the targeted alleles of the p53 gene were amplified by PCR using primers p53 -4F (5'-CGACCTCCGTTCTCTCTCCTCTCTT-3') and p53 -6R (5'-AGACGCACAAACCAAAACAAAATTACA-3'), and primers p53 -NF (5'-GCCTTCTATCGCCTTCTTGACGAGT-3') and p53 -6R, respectively.…”

Section: Methodsmentioning

confidence: 99%

Atm heterozygous deficiency enhances development of mammary carcinomas in p53heterozygous knockout mice

et al. 2004

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Introduction Ataxia-telangiectasia is an autosomal-recessive disease that affects neuro-immunological functions, associated with increased susceptibility to malignancy, chromosomal instability and hypersensitivity to ionizing radiation. Although ataxia-telangiectasia mutated (ATM) heterozygous deficiency has been proposed to increase susceptibility to breast cancer, some studies have not found excess risk. In experimental animals, increased susceptibility to breast cancer is not observed in the Atm heterozygous deficient mice (Atm +/-) carrying a knockout null allele. In order to determine the effect of Atm heterozygous deficiency on mammary tumourigenesis, we generated a series of Atm +/-mice on the p53 +/-background with a certain predisposition to spontaneous development of mammary carcinomas, and we examined the development of the tumours after X-irradiation.

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Section: Methodsmentioning

confidence: 99%

Atm heterozygous deficiency enhances development of mammary carcinomas in p53heterozygous knockout mice

et al. 2004

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“…Indeed, it has been reported that modulation of GC‐induced apoptosis was linked to p53 gene dosage. GC‐induced apoptosis was significantly enhanced in mouse thymocytes lacking one or both functional p53 alleles 14. Reciprocally, it was demonstrated that GCs protect against apoptosis induced by p53, at least in certain cellular contexts, via the modulation of Bcl‐2 protein levels 15…”

Section: Negative Regulation Of P53 and Grmentioning

confidence: 99%

Physiological and Pathological Consequences of the Interactions of the p53 Tumor Suppressor with the Glucocorticoid, Androgen, and Estrogen Receptors

Sengupta

Wasylyk

2004

Annals of the New York Academy of Sciences

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The p53 tumor suppressor plays a key role in protection from the effects of different physiological stresses (DNA damage, hypoxia, transcriptional defects, etc.), and loss of its activity has dire consequences, such as cancer. Its activity is finely tuned through interactions with other important regulatory circuits in the cell. Recently, striking evidence has emerged for crosstalk with another class of important regulators, the steroid hormone receptors, and in particular the glucocorticoid (GR), androgen (AR), and estrogen (ER) receptors. These receptors are important in maintaining homeostasis in response to internal and external stresses (GR) and in the development, growth, and maintenance of the male and female reproductive systems (AR and ER, respectively). We review how p53 interacts closely with these receptors, to the extent that they share the same E3 ubiquitin ligase, the MDM2 oncoprotein. We discuss the different physiological contexts in which such interactions occur, and also how these interactions have been undermined in various pathological situations. We will describe future areas for research, with special emphasis on GR, and how certain common features, such as cytoplasmic anchoring of p53 by the receptors, may become targets for the development of therapeutic interventions. Given the importance of GR in inflammation, erythropoiesis, and autoimmune diseases, and the importance of AR and ER in prostate and breast cancer (respectively), the studies on p53 interactions with the steroid receptors will be an important domain in the near future.

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“…Within seconds to minutes, caspases are proteolytically activated (principally 3 and 8), and the proteasome (13) cleaves key inhibitors such as p21 (Cdkn1a) and Cdc25 (14). Kinases such as the JNK stress response, Abl and Cdk2 activate signals resulting in the activation transcription factors Trp53 (15,16) or p73 (Trp73) (17), Jun (18)(19)(20)(21)(22), and Nfkb (23,24). These very early events, occurring within the first minutes of treatment, lead to the execution phase of apoptosis hours or days later.…”

Section: Introductionmentioning

confidence: 99%

Bcl2-Independent Chromatin Cleavage is a Very Early Event during Induction of Apoptosis in Mouse Thymocytes after Treatment with Either Dexamethasone or Ionizing Radiation

et al. 2003

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We have quantified the emergence of early chromatin breaks during the signal transduction phase of apoptosis in mouse thymocytes after treatment with either ionizing radiation or dexamethasone. Dexamethasone at 1 microM can induce significant levels of DNA breaks (equivalent to the amount induced directly by 7.5 Gy ionizing radiation) within 0.5 h of treatment. The execution phase of apoptosis was not observed until 4-6 h after the same treatment. The presence of the Bcl2 transgene under the control of the p56lck promoter almost completely inhibited apoptosis up to 24 h after treatment, but it had virtually no effect on the early chromatin cleavage occurring in the first 6 h. Ionizing radiation induced chromatin cleavage both directly by damaging DNA and indirectly with kinetics similar to the induction of chromatin cleavage by dexamethasone. The presence of the Bcl2 transgene had no effect on the direct or indirect radiation-induced cleavage in the first 6 h, but after the first 6 h, the Bcl2 gene inhibited further radiation-induced chromatin cleavage. These results suggest that endonucleases are activated within minutes of treatment with either dexamethasone or ionizing radiation as part of the very early signal transduction phase of apoptosis, and prior to the irreversible commitment to cell death.

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Modulations of glucocorticoid-induced apoptosis linked to the p53 deletion and to the apoptosis susceptibility gene Rapop1 (Radiation-induced apoptosis 1)

Cited by 10 publications

References 23 publications

Atm heterozygous deficiency enhances development of mammary carcinomas in p53heterozygous knockout mice

Atm heterozygous deficiency enhances development of mammary carcinomas in p53heterozygous knockout mice

Physiological and Pathological Consequences of the Interactions of the p53 Tumor Suppressor with the Glucocorticoid, Androgen, and Estrogen Receptors

Bcl2-Independent Chromatin Cleavage is a Very Early Event during Induction of Apoptosis in Mouse Thymocytes after Treatment with Either Dexamethasone or Ionizing Radiation

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