The tumor suppressor protein p53 becomes activated in response to various cellular stresses, acting as a guardian of the genome. These stressors include:
- DNA damage: This is a primary trigger for p53 activation. DNA damage can arise from factors like ionizing radiation, ultraviolet light, and chemical mutagens.
- Hypoxia: A lack of oxygen can also activate p53, prompting the cell to either adapt or undergo programmed cell death (apoptosis).
- Oncogene activation: Overactive oncogenes, which promote uncontrolled cell growth, can also lead to p53 activation.
- Ribosome biogenesis defects: Issues with ribosome formation, essential for protein synthesis, can activate p53.
- Nucleotide pool imbalances: Disruptions in the balanced supply of building blocks for DNA synthesis can also trigger p53.
- Oxidative stress: The accumulation of reactive oxygen species (ROS) within the cell can activate p53.
Upon activation, p53 triggers various cellular responses, including:
- Cell cycle arrest: p53 can halt the cell cycle at specific checkpoints, providing time for DNA repair before proceeding.
- Apoptosis: In cases of severe damage, p53 can induce programmed cell death to eliminate damaged cells and prevent tumor development.
- Senescence: p53 can also contribute to cellular senescence, a state of irreversible growth arrest.
The activation of p53 is a complex process involving post-translational modifications like phosphorylation and acetylation. These modifications enhance p53 stability and its ability to bind to DNA and regulate gene expression.
