Weinberg Florian, Schulze Ekkehard, Fatouros Chronis, Schmidt Enrico, Baumeister Ralf, Brummer Tilman
Institute of Biology III, Faculty of Biology, University of Freiburg, Germany; Centre for Biological Systems Analysis (ZBSA), Freiburg, Germany; IMMZ - Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, Germany.
Institute of Biology III, Faculty of Biology, University of Freiburg, Germany; BIOSS - Centre for Biological Signalling Studies, University of Freiburg, Germany.
Gene Expr Patterns. 2014 Jul;15(2):124-34. doi: 10.1016/j.gep.2014.05.005. Epub 2014 Jun 12.
Rio kinases are atypical serine/threonine kinases that emerge as potential cooperation partners in Ras-driven tumors. In the current study, we performed an RNAi screen in Caenorhabditis elegans to identify suppressors of oncogenic Ras signaling. Aberrant Ras/Raf signaling in C. elegans leads to the formation of a multi-vulva (Muv) phenotype. We found that depletion of riok-1, the C. elegans orthologue of the mammalian RioK1, suppressed the Muv phenotype. By using a promoter GFP construct, we could show that riok-1 is expressed in neuronal cells, the somatic gonad, the vulva, the uterus and the spermatheca. Furthermore, we observed developmental defects in the gonad upon riok-1 knockdown in a wildtype background. Our data suggest that riok-1 is a modulator of the Ras signaling pathway, suggesting implications for novel interventions in the context of Ras-driven tumors.
Rio激酶是非典型的丝氨酸/苏氨酸激酶，在Ras驱动的肿瘤中作为潜在的合作伙伴出现。在本研究中，我们在秀丽隐杆线虫中进行了RNA干扰筛选，以鉴定致癌Ras信号传导的抑制因子。秀丽隐杆线虫中异常的Ras/Raf信号传导会导致多外阴（Muv）表型的形成。我们发现，riok-1（哺乳动物RioK1的秀丽隐杆线虫同源物）的缺失抑制了Muv表型。通过使用启动子绿色荧光蛋白构建体，我们可以证明riok-1在神经细胞、体细胞性腺、外阴、子宫和受精囊中表达。此外，我们观察到在野生型背景下敲低riok-1后性腺出现发育缺陷。我们的数据表明riok-1是Ras信号通路的调节剂，这暗示了在Ras驱动的肿瘤背景下进行新型干预的可能性。
