Outline of the regulation of cellular stresses by p53.

<p>p53 protein is induced by multiple cellular stresses leading to transcriptional up-regulation of p53 target genes that are involved in regulation of apoptosis, proliferation, metabolism, and immune response. Under normal (unstressed) conditions, levels of p53 protein are tightly controlled by HDM2 E3 ubiquitin ligase, which ubiquitinates p53 leading to its proteasomal degradation. The p14ARF tumor suppressor, which functions upstream of HDM2 and p53, is required for accumulation of p53 under oncogenic stress. The role of p14ARF is to inhibit proteasomal degradation of p53 by sequestering the HDM2 protein in the nucleoli and inhibiting its E3 ligase activity.