To die or not to die: how does p53 decide?

Slee, Elizabeth A.; O’Connor, Daniel; Lü, Xin

doi:10.1038/sj.onc.1207516

Cited by 250 publications

(190 citation statements)

References 105 publications

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“…12 TP53 may also repress transcription of BCL2. 12 However, there was no change in BCL2 gene or protein expression of Reh cells after IR, indicating that this mechanism was not involved. Another candidate that might have contributed to the apoptotic phenotype of Reh cells is ID3, which was upregulated in Reh cells at 4 hr after radiation and downregulated in U698.…”

Section: Discussionmentioning

confidence: 93%

“…Induction of apoptosis has also been reported to depend on TP53 but can be induced through a number of other pathways as well. 12 Although differences in TP53 functionality have been suggested to be responsible for differences in IR-induced apoptosis and cell cycle delays among lymphoma lines, 7-9 the exact role of TP53 for the radiation response is not clear. 5,13 Tumor cells often have defects in the signal transduction for cell cycle control, DNA repair and induction of cell death that can be caused by mutations and/or amplifications/deletions of genes other than TP53.…”

mentioning

confidence: 99%

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Response of malignant B lymphocytes to ionizing radiation: Gene expression and genotype

Lyng

Landsverk

Kristiansen

et al. 2005

Intl Journal of Cancer

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The human malignant B-lymphocyte cell lines Reh and U698 show arrest in G 2 phase after ionizing radiation (IR), but only Reh cells arrest in G 1 phase and die by apoptosis. We have used cDNA microarrays to measure changes in gene expression at 2, 4 and 6 hr after irradiation of Reh and U698 cells with 0.5 and 4 Gy in order to begin exploring the molecular mechanisms underlying the phenotypic changes. We also investigated whether gene expression changes could be caused by possible aberrations of genes, as measured by comparative genomic hybridization. Reh cells showed upregulation of CDKN1A that likely mediated the G 1 arrest. In contrast, U698 cells have impaired function of TP53 protein and no activation of CDKN1A, suppressing the arrest in G 1 . The G 2 arrest in both cell lines was likely due to repression of PLK1 and/or CCNF. IR-induced apoptosis in Reh cells was probably mediated by TP53 and CDKN1A, whereas a high expression level of MCL1, caused by gene amplification, and activation of the NFKB pathway may have suppressed the apoptotic response in U698 cells. Genes suggested to be involved in apoptosis were activated long before this phenotype was detectable and showed the same temporal expression profiles as genes involved in cell cycle arrest. Our results suggest that differences in functionality and/or copy number of several genes involved in IR-regulated pathways contributed to the phenotypic differences between Reh and U698 cells after IR, and that multiple molecular factors control the radiation response of malignant B lymphocytes. ' 2005 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

Response of malignant B lymphocytes to ionizing radiation: Gene expression and genotype

Lyng

Landsverk

Kristiansen

et al. 2005

Intl Journal of Cancer

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“…The inactivation of the p53 protein is the most common strategy developed by tumour cells to evade apoptosis. p53 is central in the DNA damage response and triggers cell death by both transcription-dependent and -independent mechanisms (Slee et al, 2004;Yee and Vousden, 2005). Other examples of apoptosis evasion include disruption of Fas death receptor pathway, upregulation of the widespread antiapoptotic family of inhibitors of apoptosis proteins (IAPs) or downregulation of caspases (Muschen et al, 2000;Teitz et al, 2000;Yang et al, 2003).…”

Section: Mitochondrial Apoptosis and Its Subversion In Oncogenesismentioning

confidence: 99%

Mitochondria and cancer: is there a morphological connection?

2006

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Mitochondria are key players in several cellular functions including growth, division, energy metabolism, and apoptosis. The mitochondrial network undergoes constant remodelling and these morphological changes are of direct relevance for the role of this organelle in cell physiology. Mitochondrial dysfunction contributes to a number of human disorders and may aid cancer progression. Here, we summarize the recent contributions made in the field of mitochondrial dynamics and discuss their impact on our understanding of cell function and tumorigenesis.

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“…The p53 tumor suppressor gene plays a complex and critical role in maintaining genome integrity (Levine, 1997;Vogelstein et al, 2000;Soussi, 2000;Slee et al, 2004). Loss of p53 function increases susceptibility to malignant transformation, and mutations in the p53 tumor suppressor gene are the most common genetic abnormalities in oncology, found in >50% of all human cancers (Lutzker and Levine, 1996).…”

Section: Introductionmentioning

confidence: 99%

Ablation of a peptidyl prolyl isomerase Pin1 from p53-null mice accelerated thymic hyperplasia by increasing the level of the intracellular form of Notch1

et al. 2006

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Tumor suppressor p53 is essential for checkpoint control in response to a variety of genotoxic stresses. DNA damage leads to phosphorylation on the Ser/Thr-Pro motifs of p53, which facilitates interaction with Pin1, a pSer/pThr-Prospecific peptidyl prolyl isomerase. Pin1 is required for the timely activation of p53, resulting in apoptosis or cell cycle arrest. To investigate the physiological relationship between Pin1 and p53, we created Pin1À/Àp53À/À mice. These p53-deficient mice spontaneously developed lymphomas, mainly of thymic origin, as well as generalized lymphoma infiltration into other organs, including the liver, kidneys and lungs. Ablation of Pin1, in addition to p53, accelerated the thymic hyperplasia, but the thymocytes in these Pin1À/À p53À/À mice did not infiltrate other organs. The thymocytes in 12-week-old Pin1À/Àp53À/À mice were CD4 À CD8 À (double negative) and had significantly higher levels of the intracellular form of Notch1 (NIC) than the thymocytes of p53À/À or wild-type mice. Presenilin-1, a cleavage enzyme for NIC generation from full-length Notch1 was increased in the thymocytes of Pin1À/Àp53À/À mice. Pin1 depletion also inhibited the degradation of NIC by proteasomes. These results suggest that both Pin1 and p53 control the normal proliferation and differentiation of thymocytes by regulating the NIC level.

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To die or not to die: how does p53 decide?

Cited by 250 publications

References 105 publications

Response of malignant B lymphocytes to ionizing radiation: Gene expression and genotype

Response of malignant B lymphocytes to ionizing radiation: Gene expression and genotype

Mitochondria and cancer: is there a morphological connection?

Ablation of a peptidyl prolyl isomerase Pin1 from p53-null mice accelerated thymic hyperplasia by increasing the level of the intracellular form of Notch1

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