Drosophila Smt3 negatively regulates JNK signaling through sequestering Hipk in the nucleus
Drosophila Smt3 negatively regulates JNK signaling through sequestering Hipk in the nucleus
复制标题
果蝇 Smt3 通过将 Hipk 隔离在细胞核中负向调节 JNK 信号传导
DOI：
10.1242/dev.061770
复制
发表时间：
2011-06-15
期刊：
影响因子：
4.6
通讯作者：
Jiao, Renjie
中科院分区：
文献类型：
--
作者：
Huang, Hai;Du, Guiping;Jiao, Renjie
小泛素相关修饰物(SUMO)的翻译后修饰对多种细胞和发育过程都很重要。然而，将相扑与特定的发育信号通路联系起来的确切机制(S)仍然相对不清楚。在这里，我们证明了Smt3在果蝇翼盘中的敲除导致了类似于JNK功能获得的表型，包括异位凋亡和凋亡诱导的代偿性生长。Smt3缺失导致JNK靶基因MMP1和Pucked表达增加。我们表明，尽管同源结构域相互作用蛋白激酶(HIPK)的敲除抑制了Smt3耗尽诱导的JNK的激活，但HIPK的过表达协同增强了这种类型的JNK的激活。我们进一步证明了Hipk在体内是SUMMOL化的，并且它的核定位依赖于SUM化途径。因此，我们的结果通过Hipk的作用建立了SUMO化途径和JNK途径之间的机械联系。我们认为胞质和胞核Hipk之间的苏莫化调节平衡在调节JNK信号转导中起着至关重要的作用。
Post-translational modification by the small ubiquitin-related modifier (SUMO) is important for a variety of cellular and developmental processes. However, the precise mechanism(s) that connects sumoylation to specific developmental signaling pathways remains relatively less clear. Here, we show that Smt3 knockdown in Drosophila wing discs causes phenotypes resembling JNK gain of function, including ectopic apoptosis and apoptosis-induced compensatory growth. Smt3 depletion leads to an increased expression of JNK target genes Mmp1 and puckered. We show that, although knockdown of the homeodomain-interacting protein kinase (Hipk) suppresses Smt3 depletion-induced activation of JNK, Hipk overexpression synergistically enhances this type of JNK activation. We further demonstrate that Hipk is sumolylated in vivo, and its nuclear localization is dependent on the sumoylation pathway. Our results thus establish a mechanistic connection between the sumoylation pathway and the JNK pathway through the action of Hipk. We propose that the sumoylation-controlled balance between cytoplasmic and nuclear Hipk plays a crucial role in regulating JNK signaling.