摘要：SummaryMutations in the p53 tumor suppressor are frequent causes of cancer. Because p53 aggregates appear in some tumor cells, it has been suggested that p53 could also cause cancer by forming self-replicating protein aggregates (prions). Here, using yeast, we show that transient p53 overexpression induced the formation of p53 prion aggregates that were transmitted for >100 generations, found in lysate pellets, stained with Thioflavin T, and transmitted by cytoplasmic transfer, or transfection with lysates of cells carrying the prion or with p53 amyloid peptide. As predicted for a prion, transient interruption of p53 expression caused permanent p53 prion loss. Importantly, p53 transcription factor activity was reduced by prion formation suggesting that prion aggregation could cause cancer. p53 has also been found in liquid-like nuclear droplets in animal cell culture. In yeast, we found that liquid-like p53 foci appear in response to stress and disappear with stress removal.Graphical abstractDisplay OmittedHighlights•A published yeast model of functional nuclear human p53 tumor suppressor was used•Upon transient overexpression p53 loses its transcription function and aggregates•These p53 aggregates are cytoplasmic and behave like stable heritable prions•Stress induces p53 to form liquid-like droplets that are unstable and not prion-likeBiochemistry; Cell Biology; Cancer
