Department of Genetics and Development, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Department of Biological Sciences, University of Wisconsin, Milwaukee, WI 53201, USA.
Genetics. 2024 Sep 4;228(1). doi: 10.1093/genetics/iyae107.
Numerous factors have been implicated in the cell-cell interactions that lead to elimination of cells via cell competition, a context-dependent process of cell selection in somatic tissues that is based on comparisons of cellular fitness. Here, we use a series of genetic tests in Drosophila to explore the relative contribution of the pleiotropic cytokine tumor necrosis factor α (TNFα) in Myc-mediated cell competition (also known as Myc supercompetition or Myc cell competition). We find that the sole Drosophila TNF, Eiger (Egr), its receptor Grindelwald (Grnd/TNF receptor), and the adaptor proteins Traf4 and Traf6 are required to eliminate wild-type "loser" cells during Myc cell competition. Although typically the interaction between Egr and Grnd leads to cell death by activating the intracellular Jun N-terminal kinase (JNK) stress signaling pathway, our experiments reveal that many components of canonical JNK signaling are dispensable for cell death in Myc cell competition, including the JNKKK Tak1, the JNKK Hemipterous and the JNK Basket. Our results suggest that Egr/Grnd signaling participates in Myc cell competition but functions in a role that is largely independent of the JNK signaling pathway.
许多因素都与细胞间相互作用有关，这些相互作用导致细胞通过细胞竞争被消除，细胞竞争是一种依赖于上下文的体细胞组织中的细胞选择过程，基于细胞适应性的比较。在这里，我们使用一系列遗传测试在果蝇中探索多效细胞因子肿瘤坏死因子 α (TNFα) 在 Myc 介导的细胞竞争（也称为 Myc 超竞争或 Myc 细胞竞争）中的相对贡献。我们发现，唯一的果蝇 TNF，Eiger (Egr)，其受体 Grindelwald (Grnd/TNF 受体)，以及衔接蛋白 Traf4 和 Traf6，在 Myc 细胞竞争中被需要来消除野生型“失败者”细胞。尽管通常情况下，Egr 和 Grnd 之间的相互作用通过激活细胞内 Jun N-末端激酶 (JNK) 应激信号通路导致细胞死亡，但我们的实验表明，经典 JNK 信号通路的许多成分在 Myc 细胞竞争中的细胞死亡中是可有可无的，包括 JNKKK Tak1、JNKK Hemipterous 和 JNK Basket。我们的结果表明，Egr/Grnd 信号参与了 Myc 细胞竞争，但在很大程度上独立于 JNK 信号通路发挥作用。
