Analysis of Drosophila segmentation network identifies a JNK pathway factor overexpressed in kidney cancer
Science. 2009 Feb 27;323(5918):1218-22. Epub 2009 Jan 22.
Institute for Genomics and Systems Biology, University of Chicago and Argonne National Laboratory, Chicago, IL 60637, USA.
We constructed a large-scale functional network model in Drosophila melanogaster built around two key transcription factors involved in the process of embryonic segmentation. Analysis of the model allowed the identification of a new role for the ubiquitin E3 ligase complex factor SPOP. In Drosophila, the gene encoding SPOP is a target of segmentation transcription factors. Drosophila SPOP mediates degradation of the Jun kinase phosphatase Puckered, thereby inducing tumor necrosis factor (TNF)/Eiger-dependent apoptosis. In humans, we found that SPOP plays a conserved role in TNF-mediated JNK signaling and was highly expressed in 99% of clear cell renal cell carcinomas (RCCs), the most prevalent form of kidney cancer. SPOP expression distinguished histological subtypes of RCC and facilitated identification of clear cell RCC as the primary tumor for metastatic lesions.
Research Papers
- Conjunction of factors triggering waves of seasonal influenza
- Algorithmic Bio-surveillance For Precise Spatio-temporal Prediction of Zoonotic Emergence
- Profiling Reactive Metabolites via Chemical Trapping and Targeted Mass Spectrometry
- Does the brain listen to the gut?
- (Meta)genomic insights into the pathogenome of Cellulosimicrobium cellulans
- A robust adaptive denoising framework for real-time artifact removal in scalp EEG measurements
- Imputing Gene Expression in Uncollected Tissues Within and Beyond GTEx
- Small Rad51 and Dmc1 Complexes Often Co-occupy Both Ends of a Meiotic DNA Double Strand Break
- Controlling the Cyanobacterial Clock by Synthetically Rewiring Metabolism
- Choosing experiments to accelerate collective discovery
