The p53 tumour suppressor is one of the major apoptosis signaling pathways. The p53 protein is a nuclear transcription factor that regulates the expression of a wide variety of genes involved in apoptosis, growth arrest or senescence in response to genotoxic or cellular stress. The p53 protein levels are negatively regulated by E3 ubiquitin ligases, including MDM2. E3 ligases promote the ubiquitination and then proteasome-dependent degradation of p53. The p53 protein levels become stabilized in response to stress stimuli, including DNA damage, nucleolar stress, metabolic stress, and oncogenic stress. The p53 can promote apoptosis through interactions with Bcl-2 family proteins in the cytoplasm.