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RESEARCH PRODUCT
Cell fate regulation upon DNA damage : p53 Serine 46 kinases pave the cell death road
Thomas G. HofmannMagdalena C. Lieblsubject
Programmed cell deathCell signalingCell cycle checkpointDNA RepairDNA repairDNA damage610 MedizinApoptosisCell fate determinationBiologyGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciences0302 clinical medicine610 Medical sciencesAnimalsHumansPhosphorylation030304 developmental biology0303 health sciencesKinaseCell Cycle CheckpointsCell biologyPhosphorylationTumor Suppressor Protein p53030217 neurology & neurosurgeryDNA Damagedescription
Mild and massive DNA damage are differentially integrated into the cellular signaling networks and, in consequence, provoke different cell fate decisions. After mild damage, the tumor suppressor p53 directs the cellular response to cell cycle arrest, DNA repair, and cell survival, whereas upon severe damage, p53 drives the cell death response. One posttranslational modification of p53, phosphorylation at Serine 46, selectively occurs after severe DNA damage and is envisioned as a marker of the cell death response. However, the molecular mechanism of action of the p53 Ser46 phospho-isomer, the molecular timing of this phosphorylation event, and its activating effects on apoptosis and ferroptosis still await exploration. In this essay, the current body of evidence on the molecular function of this deadly p53 mark, its evolutionary conservation, and the regulation of the key players of this response, the p53 Serine 46 kinases, are reviewed and dissected.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-10-16 |