Pre-computed BLAST results for: gi|123983354|gb|ABM83418.1 tumor protein p53 (Li-Fraumeni syndrome) [synthetic construct]
Matching gis: 13097807;
Total (Score>106) : 942 hits in 936 proteins in 114 species
Selected: 2 hits in 2 proteins in 2 species Filter: Min Score: 106 | Included taxons: Plants;
It can activate DNA repair proteins when DNA has sustained damage.
It can also hold 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.)
It can initiate apoptosis, the programmed cell death, if the DNA damage proves to be irreparable.
p53 pathway: In a normal cell p53 is inactivated by its negative regulator, mdm2. Upon DNA damage or other stress, various pathways will lead to the dissociation of the p53 and mdm2 complex. Once activated, p53 will either induce a cell cycle arrest to allow repair and survival of the cell or apoptosis to discard the damage cell. How p53 makes this choice is currently unknown.
p53 becomes activated in response to a myriad of stress types, which include but is not limited to DNA damage (induced by either UV, IR or chemical agents,such as hydrogen peroxide), oxidative stress, osmotic shock, ribonucleotide depletion and deregulated oncogene expression. This activation is marked by two major events. Firstly, the half-life of the p53 protein is increased drastically, leading to a quick accumulation of p53 in stressed cells. Secondly, 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.
The protein kinases that are known to target this transcriptional activation domain of p53 can be roughly divided into two groups. A first group of protein kinases belongs to the MAPK family (JNK1-3, ERK1-2, p38 MAPK), which is known to respond to several types of stress, such as membrane damage, oxidative stress, osmotic shock, heat shock, etc... A second group of protein kinases (ATR, ATM, Chk1, Chk2, DNA-PK, CAK) is implicated in the genome integrity checkpoint, a molecular cascade that detects and responds to several forms of DNA damage caused by genotoxic stress.
In unstressed cells, p53 levels are kept low through a continuous degradation of p53. A protein called Mdm2 binds to p53 and transports it from the nucleus to the cytosol where it becomes degraded by the proteasome. Phosphorylation of the N-terminal end of p53 by the above-mentioned protein kinases disrupts Mdm2-binding. Other proteins, such as Pin1, are then recruited to p53 and induce a conformational change in p53 which prevents Mdm2-binding even more. Trancriptional coactivators, like p300 or PCAF, then acetylate the carboxy-terminal end of p53, exposing the DNA binding domain of p53, allowing it to activate or repress specific genes. Deacetylase enzymes, such as Sirt1 and Sirt7, can deacetylate p53, leading to an inhibition of apoptosis.
Cheng R, Ford BL, O'Neal PE, Mathews CZ, Bradford CS, Thongtan T, Barnes DW, Hendricks JD, Bailey GS. (1997, Jun.). "Zebrafish (Danio rerio) p53 tumor suppressor gene: cDNA sequence and expression during embryogenesis.". Mol Mar Biol Biotechnol.6 (2): 88–97. PMID9200835.Check date values in: |date= (help)
Lee KC, Goh WL, Xu M, Kua N, Lunny D, Wong JS, Coomber D, Vojtesek B, Lane EB, Lane DP. (2008, Jan.). "Detection of the p53 response in zebrafish embryos using new monoclonal antibodies.". Oncogene.27 (5): 629–40. PMID17684488.Check date values in: |date= (help)