Tumor-suppressor protein dynamics determine whether tissues
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Some tissues are more vulnerable to radiation damage than others. These differences involve the protein p53, a well-studied tumor-suppressor protein that initiates a cell's auto-destruct programs. Scientists explain, in vulnerable tissues, p53 levels are dynamic in nature.

Given recent studies showing that the temporal dynamics of p53 influence the fate of cultured cells in response to irradiation, the researchers set out to determine the dynamic behavior of p53 and its impact on radiation sensitivity in vivo.

Investigators 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.

Conclusively, the study proposes a mechanism for the control of radiation sensitivity and suggests tools to alter the dynamics of p53 to enhance tumor clearance. Similar approaches can be used to enhance killing of cancer cells or reduce toxicity in normal tissues following genotoxic therapies.

Nature Communications
Source: https://doi.org/10.1038/s41467-021-21145-z
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