Ma X, Xu W, Zhang D, Yang Y, Li W, Xue L
Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
Cell Death Dis. 2015 May 7;6(5):e1737. doi: 10.1038/cddis.2015.111.
The c-Jun N-terminal kinase (JNK) pathway plays essential roles in regulating a variety of cellular processes including proliferation, migration and survival. Previous genetic studies in Drosophila have identified numerous cell death regulating genes, providing new insights into the mechanisms for related diseases. Despite the known role of the small GTPase Rac1 in regulating cell death, the downstream components and underlying mechanism remain largely elusive. Here, we show that Rac1 promotes JNK-dependent cell death through Wallenda (Wnd). In addition, we find that Wnd triggers JNK activation and cell death via its kinase domain. Moreover, we show that both MKK4 and Hep are critical for Wnd-induced cell death. Furthermore, Wnd is essential for ectopic Egr- or Rho1-induced JNK activation and cell death. Finally, Wnd is physiologically required for loss of scribble-induced JNK-dependent cell death. Thus, our data suggest that wnd encodes a novel essential cell death regulator in Drosophila.
c-Jun氨基末端激酶（JNK）通路在调节包括增殖、迁移和存活在内的多种细胞过程中发挥着重要作用。先前在果蝇中的遗传学研究已经鉴定出许多细胞死亡调节基因，为相关疾病的机制提供了新的见解。尽管已知小GTP酶Rac1在调节细胞死亡中起作用，但其下游成分和潜在机制仍 largely难以捉摸。在这里，我们表明Rac1通过Wallenda（Wnd）促进JNK依赖性细胞死亡。此外，我们发现Wnd通过其激酶结构域触发JNK激活和细胞死亡。此外，我们表明MKK4和Hep对于Wnd诱导的细胞死亡都至关重要。此外，Wnd对于异位Egr或Rho1诱导的JNK激活和细胞死亡是必不可少的。最后，Wnd对于scribble缺失诱导的JNK依赖性细胞死亡在生理上是必需的。因此，我们的数据表明wnd在果蝇中编码一种新的必需细胞死亡调节因子。
