Yuezhen Xue, Nick Barker, Shawn Hoon, et al. Cancer Res 2019;79:3595-3607.
p53 protein, activated and stabilized by posttranslational modifications, performs its major functions by inducing DNA repair, cell-cycle arrest, or apoptosis through transcriptional activation. Here, we determined the ability of p53 protein stabilized via proteasome inhibition to perform similar functions as p53 induced by stresses such as DNA damage. Treating mice with the proteasome inhibitor bortezomib stabilized p53 in stem/progenitor cells of the intestine and stomach , in other proliferating tissues, and in intestinal tumors. Robust basal p53 mRNA levels were observed in the same compartments where p53 was stabilized.
This work was funded by the Agency for Science, Technology and Research (A*STAR) of Singapore. N. Barker is also supported by National Research Foundation, Prime Minister's Office, Singapore under its Investigatorship Program (Award No. NRF-NRF12017-03).
The full paper can be downloaded from the publisher's URL: https://doi.org/10.1158/0008-5472.CAN-18-3744