The Arabidopsis EDR1 Protein Kinase Negatively Regulates the ATL1 E3 Ubiquitin Ligase to Suppress Cell Death[W]
The Arabidopsis EDR1 Protein Kinase Negatively Regulates the ATL1 E3 Ubiquitin Ligase to Suppress Cell Death[W]
复制标题
DOI：
10.1105/tpc.114.131540
复制
发表时间：
2014-11
期刊：
影响因子：
11.6
通讯作者：
I. Serrano;Yangnan Gu;D. Qi;Ullrich Dubiella;R. Innes
中科院分区：
文献类型：
--
作者：
I. Serrano;Yangnan Gu;D. Qi;Ullrich Dubiella;R. Innes
ATL1 是一种泛素连接酶，可促进细胞死亡，但这种活性会受到与 ATL1 物理结合的蛋白激酶 EDR1 的抑制。 EDR1 功能的丧失会增强细胞响应生物和非生物胁迫的死亡；因此，应激诱导的细胞死亡信号传导受到两个主要且相互关联的翻译后修饰机制的调节：磷酸化和泛素化。拟南芥增强抗病性 1 (EDR1) 基因的功能丧失突变会在各种非生物和生物胁迫条件下增强程序性细胞死亡。所有 edr1 突变表型都可以通过 KEEP ON GOING 基因中的错义突变来抑制，该基因编码跨高尔基体网络/早期内体 (TGN/EE) 定位的 E3 泛素连接酶。在这里，我们报告 EDR1 与第二种 E3 泛素连接酶 ARABIDOPSIS TOXICOS EN LEVADURA1 (ATL1) 相互作用，并负向调节其活性。 ATL1 在转基因拟南芥中的过度表达会导致严重的生长抑制和细胞死亡斑块，而在本塞姆氏烟草叶子中短暂的过度表达会导致细胞死亡和组织崩溃。这两个过程都需要 ATL1 的 E3 连接酶活性。重要的是，我们发现在本塞姆氏烟草和拟南芥中，ATL1 与 TGN/EE 囊泡上的 EDR1 相互作用，并且 EDR1 抑制 ATL1 介导的细胞死亡。最后，ATL1 表达的敲低抑制了与 edr1 突变体相关的细胞死亡表型，并使拟南芥对白粉病感染高度敏感。综上所述，我们的数据表明，ATL1 是程序性细胞死亡的正调节因子，而 EDR1 负调节 TGN/EE 处的 ATL1 活性，从而控制由 ATL1 介导的泛素化事件引发的应激反应。
ATL1 is a ubiquitin ligase that promotes cell death, but this activity is inhibited by the protein kinase EDR1, which physically associates with ATL1. Loss of EDR1 function enhances cell death in response to biotic and abiotic stresses; thus, stress-induced cell death signaling is regulated by two major and interlinked posttranslational modification mechanisms: phosphorylation and ubiquitination. Loss-of-function mutations in the Arabidopsis thaliana ENHANCED DISEASE RESISTANCE1 (EDR1) gene confer enhanced programmed cell death under a variety of abiotic and biotic stress conditions. All edr1 mutant phenotypes can be suppressed by missense mutations in the KEEP ON GOING gene, which encodes a trans-Golgi network/early endosome (TGN/EE)-localized E3 ubiquitin ligase. Here, we report that EDR1 interacts with a second E3 ubiquitin ligase, ARABIDOPSIS TOXICOS EN LEVADURA1 (ATL1), and negatively regulates its activity. Overexpression of ATL1 in transgenic Arabidopsis induced severe growth inhibition and patches of cell death, while transient overexpression in Nicotiana benthamiana leaves induced cell death and tissue collapse. The E3 ligase activity of ATL1 was required for both of these processes. Importantly, we found that ATL1 interacts with EDR1 on TGN/EE vesicles and that EDR1 suppresses ATL1-mediated cell death in N. benthamiana and Arabidopsis. Lastly, knockdown of ATL1 expression suppressed cell death phenotypes associated with the edr1 mutant and made Arabidopsis hypersusceptible to powdery mildew infection. Taken together, our data indicate that ATL1 is a positive regulator of programmed cell death and EDR1 negatively regulates ATL1 activity at the TGN/EE and thus controls stress responses initiated by ATL1-mediated ubiquitination events.