Wang Xingjun, Huang Xirui, Wu Chenxi, Xue Lei
1Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092 China.
2Department of Neuroscience, Scripps Research Institute, Florida, 130 Scripps Way, Jupiter, FL USA.
Cell Death Discov. 2018 Jul 9;4:8. doi: 10.1038/s41420-018-0074-1. eCollection 2018.
Pontin (Pont), also known as Tip49, encodes a member of the AAA+ (TPases ssociated with Diverse Cellular ctivities) superfamily and plays pivotal roles in cell proliferation and growth, yet its function in cell death has remained poorly understood. Here we performed a genetic screen for dominant modifiers of Eiger-induced JNK-dependent cell death in , and identified Pont as a negative regulator of JNK-mediated cell death. In addition, loss of function of Pont is sufficient to induce cell death and activate the transcription of JNK target gene . Furthermore, the epistasis analysis indicates that Pont acts downstream of Hep. Finally, we found that Pont is also required for JNK-mediated thorax development and acts as a negative regulator of JNK phosphorylation. Together, our data suggest that encodes a negative component of Egr/JNK signaling pathway in through negatively regulating JNK phosphorylation, which provides a novel role of ATPase in Egr-JNK signaling.
Pontin（Pont），也被称为Tip49，编码AAA +（与多种细胞活动相关的三磷酸酶）超家族的一个成员，在细胞增殖和生长中起关键作用，但其在细胞死亡中的功能仍知之甚少。在这里，我们对果蝇中Eiger诱导的JNK依赖性细胞死亡的显性修饰因子进行了遗传筛选，并确定Pont是JNK介导的细胞死亡的负调节因子。此外，Pont功能的丧失足以诱导细胞死亡并激活JNK靶基因的转录。此外，上位性分析表明Pont在Hep下游起作用。最后，我们发现Pont也是JNK介导的胸部发育所必需的，并且作为JNK磷酸化的负调节因子。总之，我们的数据表明，Pont通过负调节JNK磷酸化，在果蝇中编码Egr / JNK信号通路的一个负组分，这为ATP酶在Egr - JNK信号传导中提供了一个新的作用。
