biostudies-literatureStewart-Ornstein JNCI NIH HHSNIGMS NIH HHS898https://www.ebi.ac.uk/biostudies/studies/S-EPMC7873198biostudies-literatureUnknown12(1)Radiation sensitivity varies greatly between tissues. The transcription factor p53 mediates the response to radiation; however, the abundance of p53 protein does not correlate well with the extent of radiosensitivity across tissues. Given recent studies showing that the temporal dynamics of p53 influence the fate of cultured cells in response to irradiation, we set out to determine the dynamic behavior of p53 and its impact on radiation sensitivity in vivo. We find that radiosensitive tissues show prolonged p53 signaling after radiation, while more resistant tissues show transient p53 activation. Sustaining p53 using a small molecule (NMI801) that inhibits Mdm2, a negative regulator of p53, reduced viability in cell culture and suppressed tumor growth. Our work proposes a mechanism for theNature communicationsp53 dynamics vary between tissues and are linked with radiation sensitivity.PMC7873198R00 CA207727R01 GM116864R01 GM083303Forrester WCPrytyskach MAFuret PFerretti SWeissleder RIwamoto YHolzer PKallen JLahav GMiller MAStewart-Ornstein JJambhekar Afalsep53 dynamics vary between tissues and are linked with radiation sensitivity.Radiation sensitivity varies greatly between tissues. The transcription factor p53 mediates the response to radiation; however, the abundance of p53 protein does not correlate well with the extent of radiosensitivity across tissues. Given recent studies showing that the temporal dynamics of p53 influence the fate of cultured cells in response to irradiation, we set out to determine the dynamic behavior of p53 and its impact on radiation sensitivity in vivo. We find that radiosensitive tissues show prolonged p53 signaling after radiation, while more resistant tissues show transient p53 activation. Sustaining p53 using a small molecule (NMI801) that inhibits Mdm2, a negative regulator of p53, reduced viability in cell culture and suppressed tumor growth. Our work proposes a mechanism for the2021-01-01T00:00:00Z2021 Feb2026-05-01T11:14:34.63Z2021-02-21T10:49:25ZS-EPMC78731983356397310.1038/s41467-021-21145-z