Analysis of Drosophila Segmentation Network Identifies a JNK Pathway Factor Overexpressed in Kidney Cancer

• DOI: 10.1126/science.1157669
• Publication Date: 2009-01-23T02:49:20Z
• Authors: Jiang Liu; Murad Ghanim; Lei Xue; Christopher D. Brown; Ivan Iossifov; Cesar Angeletti; Sujun Hua; Nicolas Nègre; Michael Ludwig; Thomas Stricker; Hikmat A. Al-Ahmadie; Maria Tretiakova; Robert L. Camp; Montse Perera-Alb...; David L. Rimm; Tian Xu; Andrey Rzhetsky; Kevin P. White
• Keywords: Schneider 2 cells

We constructed a large-scale functional network model in Drosophila melanogaster built around two key transcription factors involved the process of embryonic segmentation. Analysis allowed identification new role for ubiquitin E3 ligase complex factor SPOP. In Drosophila, gene encoding SPOP is target segmentation factors. mediates degradation Jun kinase phosphatase Puckered, thereby inducing tumor necrosis (TNF)/Eiger-dependent apoptosis. humans, we found that plays conserved TNF-mediated JNK signaling and was highly expressed 99% clear cell renal carcinomas (RCCs), most prevalent form kidney cancer. expression distinguished histological subtypes RCC facilitated as primary metastatic lesions.