Latest News from the “Guardian”: p53 Directly Activates Asymmetric Stem Cell Division Regulators

Since its discovery in 1979, the human tumor suppressor gene <i>TP53</i>-also known as the "guardian of the genome"-has been the subject of intense research. Mutated in most human cancers, TP53 has traditionally been considered a key fighter against stress factors by trans-activating a network of target genes that promote cell cycle arrest, DNA repair, or apoptosis. Intriguingly, over the past years, novel non-canonical functions of p53 in unstressed cells have also emerged, including the mode of stem cell division regulation. However, the mechanisms by which p53 modulates these novel functions remain incompletely understood. In a recent work, we found that <i>Drosophila</i> p53 controls asymmetric stem cell division (ASCD) in neural stem cells by transcriptionally activating core ASCD regulators, such as the conserved cell-fate determinants Numb and Brat (NUMB and TRIM3/TRIM2/TRIM32 in humans, respectively). In this short communication, we comment on this new finding, the mild phenotypes associated with <i>Drosophila p53</i> mutants in this context, as well as novel avenues for future research.