Related Experiment Video
Updated: May 1, 2026
Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
Functional analysis of the acetylation of human p53 in DNA damage responses
Sun-Ku Chung1, Shengyun Zhu, Yang Xu
1Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Abstract:
As a critical tumor suppressor, p53 is inactivated in human cancer cells by somatic gene mutation or disruption of pathways required for its activation. Therefore, it is critical to elucidate the mechanism underlying p53 activation after genotoxic and cellular stresses. Accumulating evidence has indicated the importance of posttranslational modifications such as acetylation in regulating p53 stability and activity. However, the physiological roles of the eight identified acetylation events in regulating p53 responses remain to be fully understood. By employing homologous recombination, we introduced various combinations of missense mutations (lysine to arginine) into eight acetylation sites of the endogenous p53 gene in human embryonic stem cells (hESCs). By determining the p53 responses to DNA damage in the p53 knock-in mutant hESCs and their derivatives, we demonstrate physiological importance of the acetylation events within the core domain (K120 and K164) and at the C-terminus (K370/372/373/381/382/386) in regulating human p53 responses to DNA damage.
Insights
The tumor suppressor p53
Area of Science:
- Cellular Biology
- Molecular Biology
- Cancer Research
Background:
- p53 is a critical tumor suppressor frequently inactivated in human cancers.
- Posttranslational modifications, particularly acetylation, are crucial for regulating p53 stability and activity.
- The precise physiological roles of specific p53 acetylation sites remain incompletely understood.
Purpose of the Study:
- To investigate the physiological significance of eight identified p53 acetylation sites in human cells.
- To elucidate the mechanisms of p53 activation in response to genotoxic and cellular stresses.
Main Methods:
- Utilized homologous recombination to introduce missense mutations (lysine to arginine) at eight endogenous p53 acetylation sites in human embryonic stem cells (hESCs).
- Generated p53 knock-in mutant hESCs and their derivatives.
- Assessed p53 responses to DNA damage in these engineered cell lines.
Main Results:
- Demonstrated the physiological importance of acetylation events within the p53 core domain (K120 and K164).
- Highlighted the critical role of acetylation at the C-terminus (K370/372/373/381/382/386) in regulating p53 function.
- Showcased the impact of these specific acetylation sites on human p53 responses to DNA damage.
Conclusions:
- Specific acetylation sites in the p53 core domain and C-terminus are physiologically important for regulating human p53 responses to DNA damage.
- Understanding these acetylation events provides insights into p53 tumor suppressor functions and potential therapeutic strategies for cancer.
Related Concept Videos
02:36DNA Damage Can Stall the Cell Cycle
02:36DNA Damage can Stall the Cell Cycle
02:04Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
02:23Abnormal Proliferation
01:38Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:08Nucleotide Excision Repair