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Generation of oscillations by the p53-Mdm2 feedback loop: a theoretical and experimental study.
The intracellular activity of the p53 tumor suppressor protein is regulated through a feedback loop involving its transcriptional target, mdm2. We present a simple mathematical model suggesting that,Expand
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Decision making by p53: life, death and cancer
  • M. Oren
  • Biology, Medicine
  • Cell Death and Differentiation
  • 1 April 2003
AbstractThe p53 tumor-suppressor plays a critical role in the prevention of human cancer. In the absence of cellular stress, the p53 protein is maintained at low steady-state levels and exerts veryExpand
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p53 Activates the CD95 (APO-1/Fas) Gene in Response to DNA Damage by Anticancer Drugs
Chemotherapeutic drugs cause DNA damage and kill cancer cells mainly by apoptosis. p53 mediates apoptosis after DNA damage. To explore the pathway of p53-dependent cell death, we investigated ifExpand
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Identification of a minimal transforming domain of p53: negative dominance through abrogation of sequence-specific DNA binding.
Mutations in the p53 gene are most frequent in cancer. Many p53 mutants possess transforming activity in vitro. In cells transformed by such mutants, the mutant protein is oligomerized withExpand
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DeltaN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53.
The tumor suppressor protein p53 is ubiquitously expressed as a major isoform of 53 kD, but several forms of lower molecular weight have been observed. Here, we describe a new isoform, DeltaN-p53,Expand
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Cross-talk between Akt, p53 and Mdm2: possible implications for the regulation of apoptosis
The p53 tumor suppressor protein and the Akt/PKB kinase play important roles in the transduction of pro-apoptotic and anti-apoptotic signals, respectively. We provide evidence that conflictingExpand
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Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage.
The p53 tumor-suppressor protein, a key regulator of cellular responses to genotoxic stress, is stabilized and activated after DNA damage. This process is associated with posttranslationalExpand
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MDM2 Suppresses p73 Function without Promoting p73 Degradation
ABSTRACT The newly identified p53 homolog p73 can mimic the transcriptional activation function of p53. We investigated whether p73, like p53, participates in an autoregulatory feedback loop withExpand
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Specific loss of apoptotic but not cell‐cycle arrest function in a human tumor derived p53 mutant.
The p53 tumor‐suppressor gene product is frequently inactivated in malignancies by point mutation. Although most tumor‐derived p53 mutants show loss of sequence specific transcriptional activation,Expand
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Tyrosine phosphorylation of Mdm2 by c‐Abl: implications for p53 regulation
The p53 tumor suppressor is inhibited and destabilized by Mdm2. However, under stress conditions, this downregulation is relieved, allowing the accumulation of biologically active p53. Recently weExpand
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