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Differential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Oct 31; Vol. 22 (21). Date of Electronic Publication: 2021 Oct 31. - Publication Year :
- 2021
-
Abstract
- The gene TP53 , which encodes the tumor suppressor protein p53, is mutated in about 50% of cancers. In response to cell stressors like DNA damage and after treatment with DNA-damaging therapeutic agents, p53 acts as a transcription factor to activate subsets of target genes which carry out cell fates such as apoptosis, cell cycle arrest, and DNA repair. Target gene selection by p53 is controlled by a complex regulatory network whose response varies across contexts including treatment type, cell type, and tissue type. The molecular basis of target selection across these contexts is not well understood. Knowledge gained from examining p53 regulatory network profiles across different DNA-damaging agents in different cell types and tissue types may inform logical ways to optimally manipulate the network to encourage p53-mediated tumor suppression and anti-tumor immunity in cancer patients. This may be achieved with combination therapies or with p53-reactivating targeted therapies. Here, we review the basics of the p53 regulatory network in the context of differential responses to DNA-damaging agents; discuss recent efforts to characterize differential p53 responses across treatment types, cell types, and tissue types; and examine the relevance of evaluating these responses in the tumor microenvironment. Finally, we address open questions including the potential relevance of alternative p53 transcriptional functions, p53 transcription-independent functions, and p53-independent functions in the response to DNA-damaging therapeutics.
- Subjects :
- Apoptosis genetics
DNA Repair drug effects
DNA Repair genetics
DNA, Neoplasm genetics
Humans
Neoplasms genetics
Neoplasms metabolism
Tumor Suppressor Protein p53 genetics
Antineoplastic Agents therapeutic use
Apoptosis drug effects
DNA Damage
DNA, Neoplasm metabolism
Neoplasms drug therapy
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34769259
- Full Text :
- https://doi.org/10.3390/ijms222111828