The TNF Egr participates in signaling during cell competition in the absence of a requirement for JNK

Abstract

AbstractNumerous signaling pathways have been implicated in the elimination of cells in cell competition. Here we explore the relative contributions of two of them, the recently discovered CCSM and the conserved JNK stress pathway, using a series of genetic interactions tests. We demonstrate that the expression of the TNF Eiger (Egr), and the TNFR adaptor protein Traf4, are specifically up-regulated in the wild-type “loser” cell population during Myc-mediated cell competition. We find that the absence of Egr or its receptor Grindelwald (grnd) robustly prevents elimination of the loser cells in genetic cell competition assays. In contrast, although canonical JNK signaling is activated downstream of these adaptors, loss of either of the JNK effectors Tak1/JNKK or Hemipterous/JNK is not sufficient to prevent loser cell elimination in the competitive context. Our results instead suggest that Egr/Grnd influences the Rel activator Dredd in carrying out the cells’ competitive death and elimination. Our experiments thus provide evidence that although Egr/Grnd signaling activates two parallel pathways in Myc cell competition, only the CCSM is sufficient to remove the wild-type loser cells from the tissue.