Difference between revisions of "Part:BBa K177016"

Latest revision as of 09:40, 18 October 2009

p53_CDS

Coding sequence of p53 protein originated from H.sapiens genome.

p53 is one of the most important transcription factor which in humans is encoded by the TP53 gene. This protein is important in multicellular organisms, where it regulates the cell cycle and thus act as a tumor suppressor which is responsible for cancer prevention.

p53 has several anti-cancer mechanisms:

• Activation of DNA repair proteins when it has been sustained damaged.
• Induction of growth arrest by holding the cell cycle at the G1/S regulation point on DNA damage recognition (if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle.)
• Initiation of apoptosis if the DNA damage proves to be irreparable.

Core domain of p53

Single monomer of p53 interacting with DNA

Regulation of p53 activity

p53 becomes activated in response to plethora of cellular stresses, which include inter alia DNA damage (induced by either radiation or some chemical agents), oxidative stress, osmotic shock, ribonucleotide depletion and deregulated oncogene expression. This activation is marked by two major events. At first the half-life of the p53 protein is significantly increased, leading to a fast accumulation of p53 in stressed cells. Second sign of activation is a conformational change forces p53 to take on an active role as a transcription regulator in these cells. The critical event leading to the activation of p53 is the phosphorylation of its N-terminal domain. The N-terminal transcriptional activation domain contains a large number of phosphorylation sites and can be considered as the primary target for protein kinases transducing stress signals.

Sequence and Features