To the extent possible under law, AOP-Wiki has waived all copyright and related or neighboring rights to KE:1974
Key Event Title
Activation of Tumor Protein 53
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Increased DNA damages during embryonic development lead to microcephaly||KeyEvent||Brendan Ferreri-Hanberry (send email)||Under development: Not open for comment. Do not cite|
Key Event Description
TP53 is a key player in protecting the integrity of the genome. TP53 protein is present at low levels in all type of cells but become stabilized and transcriptionally active after exposures to DNA-damaging agents. The increase level of TP53 after exposure to ionizing radiation or other stress is primarily regulated at the post-translational level (Kastan MB, Onyekwere O, Sidransky D, Vogelstein B and Craig RW (1991) Cancer Res. 51: 6304–6311.). In response to DNA double-strand breaks activated ATM mediates phosphorylation at multiple sites on p53 including ser 6, 9, 15, 20, 46 and Thr 18 (Saito S, Goodarzi AA, Higashimoto Y, Noda Y, Lees-Miller SP, Appella E and Anderson CW (2002) J. Biol. Chem. 277: 12491–12494.). The phosphorylated P53 escape proteosomal degradation mediated in non stress situation by MDM2, and thus leads to stabilization of the protein (Jackson MW and Berberich SJ (2000) Mol. Cell. Biol. 20: 1001–1007.)
How It Is Measured or Detected
Antibody against phosphorylated TP53 are used to detect the activated form of TP53. This is made by immunocytochemistry techniques through Western Blot analysis on protein extract or by immunocytochemistry on tissue sections.
Domain of Applicability
Somatic and proliferating cells
Consequence of increased and irreparable DNA damages
Kashiwagi, Hiroki, Kazunori Shiraishi, Kenta Sakaguchi, Tomoya Nakahama, and Seiji Kodama. 2018. “Repair Kinetics of DNA Double-Strand Breaks and Incidence of Apoptosis in Mouse Neural Stem/Progenitor Cells and Their Differentiated Neurons Exposed to Ionizing Radiation.” Journal of Radiation Research 59 (3): 261–71. https://doi.org/10.1093/jrr/rrx089.
Limoli, Charles L., Erich Giedzinski, Radoslaw Rola, Shinji Otsuka, Theo D. Palmer, and John R. Fike. 2004. “Radiation Response of Neural Precursor Cells: Linking Cellular Sensitivity to Cell Cycle Checkpoints, Apoptosis and Oxidative Stress.” Radiation Research 161 (1): 17–27. https://doi.org/10.1667/rr3112.
Kastan MB, Onyekwere O, Sidransky D, Vogelstein B and Craig RW (1991) Cancer Res. 51: 6304–6311
Saito S, Goodarzi AA, Higashimoto Y, Noda Y, Lees-Miller SP, Appella E and Anderson CW (2002) J. Biol. Chem. 277: 12491–12494
Jackson MW and Berberich SJ (2000) Mol. Cell. Biol. 20: 1001–1007