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p53 Signaling

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Description

p53 is a tumour suppressor protein that regulates the expression of a wide variety of genes involved in Apoptosis, Growth arrest, Inhibition of cell cycle progression, Differentiation and accelerated DNA repair or Senescence in response to Genotoxic or Cellular Stress. As a transcription factor, p53 is composed of an N-terminal Activation Domain, a central specific DNA Binding Domain, and a C-terminal Tetramerization Domain, followed by a Regulatory Domain rich in basic Amino acids. Having a short half-life, p53 is normally maintained at low levels in unstressed mammalian cells by continuous ubiquitylation and subsequent degradation by the 26S Proteasome. Nonphosphorylated p53 is ubiquitylated by the MDM2 (Mouse Double Minute-2) ubiquitin ligase. MDM2 binding inactivates p53 by two mechanisms. First, MDM2 binds to the transactivation domain of p53, precluding interaction with the transcriptional machinery. Second, this [...]

References:

1.Distribution of p53 mutations in esophageal and gastric carcinomas and the relationship with p53 expression.
Hanazono K, Natsugoe S, Stein HJ, Aikou T, Hoefler H, Siewert JR.
Oncol Rep. 2006 Apr;15(4):821-4.
2.Mdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells in vivo.
Francoz S, Froment P, Bogaerts S, De Clercq S, Maetens M, Doumont G, Bellefroid E, Marine JC.
Proc Natl Acad Sci U S A. 2006 Feb 21;
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