Wild-type p53 does not directly induce the senescent phenotype it induces cell-cycle arrest, which then converts to senescence (geroconversion) without any p53 assistance.
To be precise, as noticed in the commentary, there were only two, not three, independent tumor-suppressing activities of p53 known at that time: namely, (i) apoptosis and (ii) cell-cycle arrest/senescence. Mutant p53 (p53-3KR), constructed by Li et al., lacking all three then-known tumor-suppressing activities, still suppressed tumors. This actually was predicted in 2012 in the commentary entitled, “Tumor suppression by p53 without apoptosis and senescence: conundrum or rapalog-like gerosuppression?” The commentary was written on another fascinating paper by the same senior author Gu and co-workers (Li et al.), “Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence.” Recent work by Gu and co-workers (Kon et al., published in 2021), entitled, “mTOR inhibition acts as an unexpected checkpoint in p53-mediated tumor suppression,” seemingly “unexpectedly” demonstrated in mice that the ability of p53 to suppress mTOR is essential for tumor suppression early in life.
Blagosklonny published a new research commentary in Oncoscience ( Volume 9) on August 30, 2022, entitled, “ As expected, based on rapamycin-like p53-mediated gerosuppression, mTOR inhibition acts as a checkpoint in p53-mediated tumor suppression.” “SASP is one of the mechanisms of tumor-promotion by senescent cells and is inhibited by both rapamycin and p53. Image: Rapamycin-like gerosuppression by p53.
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