p53 inhibitors prevent activity of p53 proteins. p53 is the tumor suppressor that regulates the expression of p53 upregulated modulator of apoptosis (PUMA). PUMA is involved in p53-dependent and –independent apoptosis induced by a variety of signals, and is regulated by transcription factors, not by post-translational modifications. P53 is a major orchestrator of the cellular response to a broad array of stress types by regulating apoptosis, cell cycle arrest, senescence, DNA repair and genetic stability. After activation, PUMA interacts with the multidomain Bcl-2 family members to signal apoptosis to the mitochondria by inducing outer membrane permeabilization.
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