title: Analysis of Drosophila segmentation network identifies a JNK pathway factor overexpressed in kidney cancer.
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.
authors.affiliation: Institute for Genomics and Systems Biology, University of Chicago and Argonne National Laboratory, Chicago, IL 60637, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.forename: Murad
authors.initials: M
authors.lastname: Ghanim
authors.forename: Lei
authors.initials: L
authors.lastname: Xue
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Brown
authors.forename: Ivan
authors.initials: I
authors.lastname: Iossifov
authors.forename: Cesar
authors.initials: C
authors.lastname: Angeletti
authors.forename: Sujun
authors.initials: S
authors.lastname: Hua
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nègre
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.forename: Thomas
authors.initials: T
authors.lastname: Stricker
authors.forename: Hikmat A
authors.initials: HA
authors.lastname: Al-Ahmadie
authors.forename: Maria
authors.initials: M
authors.lastname: Tretiakova
authors.forename: Robert L
authors.initials: RL
authors.lastname: Camp
authors.forename: Montse
authors.initials: M
authors.lastname: Perera-Alberto
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
authors.forename: Tian
authors.initials: T
authors.lastname: Xu
authors.forename: Andrey
authors.initials: A
authors.lastname: Rzhetsky
authors.forename: Kevin P
authors.initials: KP
authors.lastname: White
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D054910:Compound Eye, Arthropod / Q000196:embryology / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D051717:Fushi Tarazu Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029721:Drosophila Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C509761:SPOP protein, human; D014157:Transcription Factors; C052837:eve protein, Drosophila; C497169:ftz protein, Drosophila; D053612:Janus Kinases; C110854:puc protein, Drosophila; D010749:Phosphoprotein Phosphatases