אסיף מאגר המחקר החקלאי

Analysis of Drosophila segmentation network identifies a JNK pathway factor overexpressed in kidney cancer

Year:

2009

Source of publication :

Authors :

Volume :

323

Co-Authors:

Liu, J., Institute for Genomics and Systems Biology, University of Chicago, Argonne National Laboratory, Chicago, IL 60637, United States, Department of Human Genetics, University of Chicago, Chicago, IL 60637, United States
Ghanim, M., Institute for Genomics and Systems Biology, University of Chicago, Argonne National Laboratory, Chicago, IL 60637, United States, Department of Human Genetics, University of Chicago, Chicago, IL 60637, United States, Department of Entomology, Volcani Center, Bet Dagan, Israel
Xue, L., Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06519, United States
Brown, C.D., Institute for Genomics and Systems Biology, University of Chicago, Argonne National Laboratory, Chicago, IL 60637, United States, Department of Human Genetics, University of Chicago, Chicago, IL 60637, United States
Iossifov, I., Institute for Genomics and Systems Biology, University of Chicago, Argonne National Laboratory, Chicago, IL 60637, United States, Department of Medicine, University of Chicago, Chicago, IL 60637, United States, Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11742, United States
Angeletti, C., Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, United States
Hua, S., Institute for Genomics and Systems Biology, University of Chicago, Argonne National Laboratory, Chicago, IL 60637, United States, Department of Human Genetics, University of Chicago, Chicago, IL 60637, United States
Nègre, N., Institute for Genomics and Systems Biology, University of Chicago, Argonne National Laboratory, Chicago, IL 60637, United States, Department of Human Genetics, University of Chicago, Chicago, IL 60637, United States
Ludwig, M., Institute for Genomics and Systems Biology, University of Chicago, Argonne National Laboratory, Chicago, IL 60637, United States, Department of Human Genetics, University of Chicago, Chicago, IL 60637, United States, Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637, United States
Stricker, T., Institute for Genomics and Systems Biology, University of Chicago, Argonne National Laboratory, Chicago, IL 60637, United States, Department of Human Genetics, University of Chicago, Chicago, IL 60637, United States, Department of Pathology, University of Chicago, Chicago, IL 60637, United States
Al-Ahmadie, H.A., Department of Pathology, University of Chicago, Chicago, IL 60637, United States
Tretiakova, M., Department of Pathology, University of Chicago, Chicago, IL 60637, United States
Camp, R.L., Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, United States
Perera-Alberto, M., Department of Anatomy, La Laguna University, La Laguna, 38320 Tenerife, Spain
Rimm, D.L., Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, United States
Xu, T., Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06519, United States
Rzhetsky, A., Institute for Genomics and Systems Biology, University of Chicago, Argonne National Laboratory, Chicago, IL 60637, United States, Department of Medicine, University of Chicago, Chicago, IL 60637, United States
White, K.P., Institute for Genomics and Systems Biology, University of Chicago, Argonne National Laboratory, Chicago, IL 60637, United States, Department of Human Genetics, University of Chicago, Chicago, IL 60637, United States, Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637, United States

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Abstract:

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.

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