p53 dynamics vary between tissues and are linked with radiation sensitivity

• DOI: 10.1038/s41467-021-21145-z
• Publication Date: 2021-02-09T21:23:32Z
• Authors: Jacob Stewart-Orn...; Yoshiko Iwamoto; Miles A. Miller; Mark A. Prytyskach; Stephane Ferretti; Philipp Holzer; Joerg Kallen; Pascal Furet; Ashwini Jambhekar; William C. Forrester; Ralph Weissleder; Galit Lahav
• Keywords: Radiosensitivity; Radiation sensitivity; Bystander effect; Dynamics

Abstract Radiation sensitivity varies greatly between tissues. The transcription factor p53 mediates the response to radiation; however, abundance of protein does not correlate well with extent radiosensitivity across Given recent studies showing that temporal dynamics influence fate cultured cells in irradiation, we set out determine dynamic behavior and its impact on radiation vivo. We find radiosensitive tissues show prolonged signaling after radiation, while more resistant transient activation. Sustaining using a small molecule (NMI801) inhibits Mdm2, negative regulator p53, reduced viability cell culture suppressed tumor growth. Our work proposes mechanism for control suggests tools alter enhance clearance. Similar approaches can be used killing cancer or reduce toxicity normal following genotoxic therapies.