Hypoxia

Nitric oxide

Temperature shock

UV radiation rNTP depletion

ionizing radiation

p53 degradation

pro inflammatory cytokines

DNA damage

Inhibition of Angiogenesis and metastasis

homodimerisation

transription DNA repair cell cycle arrest

Apoptosis

The p53 pathway responds to stresses, both internal and external to the cell, that can disrupt the fidelity of DNA replication and cell division. Stress signals, such as those triggered by gamma or UV radiation, base alkylation, depurination of DNA or oxidative free radicals, are transmitted to p53 by proteins that post-translationally modify it. These modifications result in the activation of the p53 protein as a transcription factor that can initiate cell cycle arrest, cellular senescence or apoptosis via its switching on cascades of p53-responsive genes. The deleterious effects of intrinsic or extrinsic stresses, which could result in aberrant DNA replication, genome instability or anomalies in chromosome segregation, are accommodated (cell cycle arrest and DNA repair) or, alternatively, eliminated (apoptosis) by the p53 pathway in this way. In addition to these responses at the single-cell level, the p53 pathway of one cell can communicate with neighbouring cells by triggering the secretion of proteins that may alter the cellular environment. For example, p53 pathway-secreted proteins can alter the extracellular matrix and influence angiogenic signals in a localized region of tissue. Overall, the p53 pathway plays an important role in our understanding of cancer as its loss-of-function is a common feature of human cancers.