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Citation
Liu, J., Ghanim, M., Xue, L., Brown, C.D., Iossifov, I., Angeletti, C., Hua, S., Nègre, N., Ludwig, M., Stricker, T., Al-Ahmadie, H.A., Tretiakova, M., Camp, R.L., Perera-Alberto, M., Rimm, D.L., Xu, T., Rzhetsky, A., White, K.P. (2009). Analysis of Drosophila segmentation network identifies a JNK pathway factor overexpressed in kidney cancer.  Science 323(5918): 1218--1222.
FlyBase ID
FBrf0207535
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC2756524 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
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    Publication Type
    Journal
    Abbreviation
    Science
    Title
    Science
    Publication Year
    1895-
    ISBN/ISSN
    0036-8075
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    Genes (22)
    Physical Interactions (9)
    Cell Lines (1)