Analysis of double-stranded RNA-induced apoptosis pathways using interferon-response noninducible small interfering RNA expression vector library.
We have developed an original vector library that allowed us to exploit the phenomenon of RNA interference but also allowed us to avoid the confounding effects of the interferon response. In the present work, we used our library of small interfering RNA expression vectors to examine the genes involved in apoptosis that was induced by double-stranded RNA. To our surprise, screening of our library revealed two novel double-stranded RNA-induced apoptotic pathways, a JNK/SAPK-mediated mitochondrial pathway and an ERK2-related pathway, both of which appeared to be independent of the serine-threonine protein kinase-dependent caspase pathway. We also found that MST2 and protein kinase Calpha both activated the pro-apoptotic signal mediated by ERK2. The results of our screening analysis suggested the utility of large scale screenings with libraries of small interfering RNA expression vectors.
Matsumoto
Sahohime
S
Department of Chemistry and Biotechnology, School of Engineering, the University of Tokyo, Hongo, Tokyo 113-8656.
Miyagishi
Makoto
M
Akashi
Hideo
H
Nagai
Ryozo
R
Taira
Kazunari
K
D017209:Apoptosis / Q000235:genetics*; D015723:Gene Library; D005820:Genetic Testing / Q000379:methods; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000235:genetics*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D012330:RNA, Double-Stranded; D008156:Luciferases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases