TY - JOUR
T1 - Analysis of Drosophila segmentation network identifies a JNK pathway factor overexpressed in kidney cancer
AU - Liu, Jiang
AU - Ghanim, Murad
AU - Xue, Lei
AU - Brown, Christopher D.
AU - Iossifov, Ivan
AU - Angeletti, Cesar
AU - Hua, Sujun
AU - Nègre, Nicolas
AU - Ludwig, Michael
AU - Stricker, Thomas
AU - Al-Ahmadie, Hikmat A.
AU - Tretiakova, Maria
AU - Camp, Robert L.
AU - Perera-Alberto, Montse
AU - Rimm, David L.
AU - Xu, Tian
AU - Rzhetsky, Andrey
AU - White, Kevin P.
PY - 2009/2/27
Y1 - 2009/2/27
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=60349085402&partnerID=8YFLogxK
U2 - 10.1126/science.1157669
DO - 10.1126/science.1157669
M3 - Article
C2 - 19164706
AN - SCOPUS:60349085402
SN - 0036-8075
VL - 323
SP - 1218
EP - 1222
JO - Science
JF - Science
IS - 5918
ER -