Differential Transcriptional Regulation of Polymorphic p53 Codon 72 in Metabolic Pathways
| Autor: | Seo-Young Lee, Sun-Ku Chung, Bu-Yeo Kim |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
induced pluripotent stem cell
Cell cycle checkpoint QH301-705.5 DNA damage Induced Pluripotent Stem Cells Cell fate determination Biology Polymorphism Single Nucleotide Article Catalysis Inorganic Chemistry polymorphic p53 codon 72 Transcriptional regulation Humans Biology (General) Physical and Theoretical Chemistry Codon Induced pluripotent stem cell QD1-999 Molecular Biology Transcription factor Gene Cells Cultured Spectroscopy Gene Expression Profiling metabolic signaling pathway Organic Chemistry apoptosis General Medicine DNA damage stress Computer Science Applications Cell biology Chemistry growth arrest Gene Expression Regulation Apoptosis Tumor Suppressor Protein p53 Biomarkers Metabolic Networks and Pathways |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 10793, p 10793 (2021) Volume 22 Issue 19 |
| ISSN: | 1422-0067 |
| Popis: | p53 is a transcription factor that is activated under DNA damage stress and regulates the expression of proapoptotic genes including the expression of growth arrest genes to subsequently determine the fate of cells. To investigate the functional differences of polymorphic p53 codon 72, we constructed isogenic lines encoding each polymorphic p53 codon 72 based on induced pluripotent stem cells, which can endogenously express each polymorphic p53 protein only, encoding either the arginine 72 (R72) variant or proline 72 (P72) variant, respectively. We found that there was no significant functional difference between P72 and R72 cells in growth arrest or apoptosis as a representative function of p53. In the comprehensive analysis, the expression pattern of the common p53 target genes, including cell cycle arrest or apoptosis, was also increased regardless of the polymorphic p53 codon 72 status, whereas the expression pattern involved in metabolism was decreased and more significant in R72 than in P72 cells. This study noted that polymorphic p53 codon 72 differentially regulated the functional categories of metabolism and not the pathways that determine cell fate, such as growth arrest and apoptosis in cells exposed to genotoxic stress. |
| Databáze: | OpenAIRE |
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