Once p53 has detected DNA damage due to mutations, it will decide whether the cell’s next step is apoptosis or cell repair.
Apoptosis, coordinated cell death, is one of the main controls for p53 tumor suppressor capability and increasing cell response to chemotherapy.
p53 can increase transcription of apoptotic genes such as Bcl-2 and BH3-only genes. The protein will bind to consensus sequences on these genes DNA segment and will induce Bcl-2 protein formation. Bcl-2 protein will then increase mitochondria apoptosis proteins.
p53 can increase caspase-6 protein production by binding to caspase-6 gene. Caspase-6 functions to increase cell reactivity to chemotherapy drugs.
p53 can increase sensitivity of cells to death receptor ligands and will thus encourage apoptosis directly and indirectly ( by means of “encouraging cell death in ligand rich environment” ) (Fridman)
p53 can be used as a gene response element, in which a minimal level of the protein will cause a protein to be induced.
ex. p-53 response gene, PIDD, is activated and will encourage cell apoptosis
p53 can increase ROS, reactive oxygen species, which will overall interrupt redox reactions within cell and cause mitochonidrial dysfunction to initiate cell apoptosis.
p53 can repress anti-apoptotic and mitotic genes
ex. Survivin, which as been implicated and over-expressed in many cancers
References
- Fridman, J., Lowe, S. Control of apoptosis by p53. Oncogene 22, 9030–9040 (2003). https://doi.org/10.1038/sj.onc.1207116
Spring 2020 Cell Cycle and Cancer 