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 Printable version |
p53 activation by PI-3K family kinases after DNA double-strand breaks |
Bulletin du Cancer. Volume 87, Number 9, 635-41, Septembre 2000, Synthèses
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 Résumé
Article gratuit
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Author(s) : David Pernin, Nancy Uhrhammer, Pierre Verrelle, Yves-Jean Bignon, Jacques-Olivier Bay |
Summary : p53 plays a central role in the cellular response to DNA double-strand breaks (DSBs), and to DNA damage in general. The protein kinases ATM, ATR and DNA-PK detect DSBs and transmit this information to p53 by phosphorylation. This phosphorylation dissociates p53 from its negative regulator, mdm2. p53 then undergoes further modification and activates transcription of the genes responsible for cell cycle arrest. In certain circumstances, p53 also activates transcription of the genes responsible for apoptosis. The dysfunction of this cascade of events is oncogenic, with P53 itself being the most commonly mutated gene in malignant cells, although mutations in both the DNA damage sensors and cell cycle checkpoint and apoptosis effectors are frequent. A more complete understanding of p53 and the proteins it interacts with may allow the development of new cancer treatments. |
Keywords : DNA damage, p53, ATM, DNA-PK, ATR, phosphorylation. |
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