Specific loss of apoptotic but not cell - cycle arrest function in a human tumor derived p53 mutant (original) (raw)
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Apoptosis, cancer and the p53 tumour suppressor gene
Cancer and Metastasis Reviews, 1995
One of the most commonly detected abnormalities in human cancer is mutation of the p53 tumour suppressor gene. Intrinsic to the function of p53 is its ability to induce apoptotic cell death and to cause cell cycle arrest. Moreover, p53 plays an important role in controlling the cellular response to DNA damaging agents such as ionizing radiation and cancer chemotherapeutic drugs. Loss of p53 function causes increased resistance to radiation and chemotherapeutic agents, and there is increasing evidence that p53 mutational status is an important determinant of clinical outcome in cancer. This review will focus on recent data describing the biochemistry of p53 function, its role in mediating apoptosis and cell cycle arrest and in the control of tumour growth and death.
The p53 tumour suppressor gene: a mediator of a G1 growth arrest and of apoptosis
Experientia, 1996
The turn0ur suppressor gene p53 plays a major role in the protection of cells from DNA damage. Activation of the protein in response to irradiation or genotoxic agents, and possibly by other signals, results in growth arrest at the G1 phase of the cell cycle or in apoptosis. While it has been shown that the ability of p53 to function as a sequence-specific transcriptional activator is necessary for the induction of growth arrest, the meChanism of p53-mediated apoptosis is not yet clear. It appears that under some conditions activation of the G1 checkpoint will prevent apoptosis, but the cellular environment may alter the result of p53 activation towards cell death, p53 may also directly induce apoptosis through several pathways, which may be transcriptionally dependent or independent. The outcome -a G1 arrest or apoptosis -will depend on a complex network of regulatory signals.
P53 Protein and Its Fundamental Role in the Cell Cycle, Apoptosis and Cancer
Enciclopédia Biosfera, 2018
P53 is activated in response to DNA damage, hypoxia, oncogenesis expression to promote the cell cycle checkpoints, DNA repair, cell senescence and apoptosis. These activities are important for the suppression of tumor formation and mediate cellular responses that are related to the cell cycle control, being the key element and also the main obstacle to the suppression of tumors. A better understanding of the apoptotic mechanism of p53 may promote the development of in vitro and in vivo assays, contributing to improve cancer diagnosis and prognosis and also helping with the deployment of rational strategies that advance the treatment therapies. In this way, this review is intended to present the effects of p53 protein on cells and show how it works on the activation of specific genes to promote the cell control and regulation and clarify the mysteries evolving the cell regulation mediated by p53 protein.
Seminars in Cancer Biology, 1998
One of the several biological functions attributed to p53 is the ability to induce apoptotic cell suicide. It has become clear that this apoptotic activity of p53 is central to its role as a tumor suppressor. A summary of current knowledge concerning the mechanisms of p53-mediated apoptosis is presented. The pivotal ' choice' between p53-induced viable growth arrest and apoptosis is discussed.
Blood, 1995
Employing the myeloblastic leukemia M1 cell line, which does not express endogenous p53, and genetically engineered variants, it was recently shown that activation of p53, using a p53 temperature-sensitive mutant transgene (p53ts), resulted in rapid apoptosis that was delayed by high level ectopic expression of bcl-2. In this report, advantage has been taken of these M1 variants to investigate the relationship between p53-mediated G1 arrest and apoptosis. Flow cytometric cell cycle analysis has provided evidence that activation of wild-type (wt) p53 function in M1 cells resulted in the induction of G1 growth arrest; this was clearly seen in the M1p53/bcl-2 cells because of the delay in apoptosis that unmasked p53-induced G1 growth arrest. This finding was further corroborated at the molecular level by analysis of the expression and function of key cell cycle regulatory genes in M1p53 versus M1p53/bcl-2 cells after the activation of wt p53 function; events that take place at early ti...
The dark side of a tumor suppressor: anti-apoptotic p53
Cell Death and Differentiation, 2008
Depending on multiple factors DNA damage leads either to cell cycle arrest or apoptosis. One of the main players deciding the fate of a cell is the tumor suppressor p53 that modulates these responses in a transcription-dependent and -independent manner. Over the past few years, however, strong evidence accumulated that p53 engages also powerful pro-survival pathways by transcriptionally activating a multitude of genes whose products efficiently counteract apoptosis. Our review summarizes the current knowledge concerning approximately forty p53-regulated proteins that exert their anti-apoptotic potential by interfering with diverse cellular processes. These activities are surely essential for normal development and maintenance of a healthy organism, but may easily turn into the dark side of the tumor suppressor p53 contributing to tumorigenesis.