ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins

@article{Waterman1998ATMdependentAO,
  title={ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins},
  author={Matthew James Fish Waterman and Elena S. Stavridi and Jennifer L. F. Waterman and Thanos D Halazonetis},
  journal={Nature Genetics},
  year={1998},
  volume={19},
  pages={175-178}
}
The p53 tumour-suppressor protein is a sequence-specific DNA-binding transcription factor that induces cell cycle arrest or apoptosis in response to genotoxic stress. Activation of p53 by DNA-damaging agents is critical for eliminating cells with damaged genomic DNA and underlies the apoptotic response of human cancers treated with ionizing radiation (IR) and radiomimetic drugs. The molecular mechanisms by which DNA damage activates p53 have not been elucidated. Both the levels of p53 protein… 
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TLDR
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Role of p53 in Regulation of Death Receptors
TLDR
This chapter reviews how p53 is activated, and how it emits a signal in response to DNA damage and death receptors induced by p53.
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TLDR
The nature of p53 modifications, the enzymes that bring them about, and how changes in p53 modification lead to p53 activation are discussed are discussed.
DNA damage‐inducible phosphorylation of p53 at Ser20 is required for p53 stabilization
TLDR
The data showed that the mutant p53 was clearly defective for full stabilization of p53 in response to DNA damage, and concluded that Ser20 phosphorylayion is critical for modulating the negative regulation of p54 by Mdm2, probably through phosphorylation‐dependent inhibition of p 53‐Mdm2 interaction in the physiological context.
Substitutions that compromise the ionizing radiation-induced association of p53 with 14-3-3 proteins also compromise the ability of p53 to induce cell cycle arrest.
TLDR
These p53 mutants retained sequence-specific DNA binding activity, but their ability to activate transcription of the endogenous p21/waf1/cip1 gene and to induce G(1) arrest was compromised, suggesting that the dephosphorylation of Ser(376) and the association of p53 with 14-3-3 proteins contribute to the activation of p 53 in response to IR.
The onset of p53-dependent DNA repair or apoptosis is determined by the level of accumulated damaged DNA.
TLDR
It is shown that the treatment of cells with low doses of gamma-irradiation or cisplatin resulted in an immediate enhancement of p53-dependent DNA repair, measured by base excision repair (BER) activity, and that the decision of cells to induce a p 53- dependent DNA repair or apoptosis is most probably controlled by the level of genotoxic agent introduced to cells.
Mechanistic differences in the transcriptional activation of p53 by 14-3-3 isoforms
TLDR
The results suggest that structurally and functionally similar 14-3-3 isoforms may exert their regulatory potential on p53 through different mechanisms.
Regulation of p53 downstream genes.
TLDR
The p53 tumor suppressor is the most commonly mutated gene in human cancer and its activation of expression of a number of target genes including p21WAFI, GADD45, 14-3-3 sigma, bax, Fas/APO1, KILLER/DR5, PIG3, Tsp1, IGF-BP3 and others are reviewed.
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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