A potential link between p53, cell competition and ribosomopathy in mammals and in Drosophila

Abstract

The term cell competition has been used to describe the phenomenon whereby particular cells can be eliminated during tissue growth only when more competitive cells are available to replace them. Multiple examples implicate differential activity of p53 in cell competition in mammals, but p53 has not been found to have the same role in Drosophila, where the phenomenon of cell competition was first recognized. Recent studies now show that Drosophila cells harboring mutations in Ribosomal protein (Rp) genes, which are eliminated by cell competition with wild type cells, activate a p53 target gene, Xrp1. In Diamond Blackfan Anemia, human Rp mutants activate p53 itself, through a nucleolar stress pathway. These results suggest a link between mammalian and Drosophila Rp mutants, translation, and cell competition.

Cooperation between oncogenic Ras and wild-type p53 stimulates STAT non-cell autonomously to promote tumor radioresistance

“…Developmental and regenerative signaling contexts may functionalize p53 in a similar manner to maintain tissue homeostasis. Neighboring cells with different levels of wild-type p53 influence the growth of other cells in Drosophila and mammalian tissues 84 .…”

The transcription factor Xrp1 orchestrates both reduced translation and cell competition upon defective ribosome assembly or function

“…P53 is responsible for at least some consequences of Rp haploinsufficiency in mice, perhaps even including the reduction in translation(Tiu et al, 2020). P53 is also implicated in cell competition in mammals, although not in Drosophila , where Xrp1 may acquire some of its functions(Kale, Li, Lee, & Baker, 2015; Baker, Kiparaki, & Khan, 2019). In Drosophila it seems that RpS12 is particularly critical for activating Xrp1, through an unknown mechanism(Kale et al, 2018; Boulan, Andersen, Colombani, Boone, & Leopold, 2019; Ji et al, 2019).…”

FGF21 Induced by the ASK1-p38 Pathway Promotes Mechanical Cell Competition by Attracting Cells

“…Given these data, FGF21 might induce the compaction of scrib KD cells, which further enhances p38 activation and accelerates upregulation of p53. As the significance of p53 in cell competition has also attracted attention in other cell competition models, [29][30][31][32] clarifying the relationship between p53 and FGF21 is an important question for future studies. It would also be interesting to determine whether mechanical compaction further increases the expression of FGF21 through p38 activation in scrib KD cells.…”