Abstract：
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 ⍺ (TNF⍺) in Myc-mediated cell competition (also known as Myc super-competition or Myc cell competition). We find that the sole Drosophila TNF, Eiger (Egr), its receptor Grindelwald (Grnd/TNFR), 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 (Hep) and the JNK Basket (Bsk). 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.
摘要：
细胞间相互作用涉及许多因素，这些因素导致通过细胞竞争消除细胞。基于细胞适应性比较的体细胞组织中细胞选择的上下文相关过程。在这里，我们使用果蝇的一系列遗传测试来探索多效细胞因子肿瘤坏死因子(TNF)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/TNFR），在Myc细胞竞争过程中，需要衔接蛋白Traf4和Traf6来消除野生型“失败者”细胞。尽管Egr和Grnd之间的相互作用通常通过激活细胞内JunN末端激酶（JNK）应激信号通路导致细胞死亡，我们的实验表明，在Myc细胞竞争中，规范JNK信号的许多组成部分对于细胞死亡是可有可无的，包括JNKKKTak1，JNKK半翅目（Hep）和JNK篮子（Bsk）。我们的结果表明，Egr/Grnd信号参与Myc细胞竞争，但其作用在很大程度上独立于JNK信号通路。
