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161.
Kristoffer von Stedingk Jan Koster Marta Piqueras Rosa Noguera Samuel Navarro Sven Påhlman Rogier Versteeg Ingrid Øra David Gisselsson David Lindgren Håkan Axelson 《Translational oncology》2013,6(4):447-IN6
Amplification of the MYCN oncogene is strongly associated with poor prognosis in neuroblastoma (NB). In addition to MYCN amplification, many studies have focused on identifying patients with a poor prognosis based on gene expression profiling. The majority of prognostic signatures today are comprised of large gene lists limiting their clinical application. In addition, although of prognostic significance,most of these signatures fail to identify cellular processes that can explain their relation to prognosis. Here, we determined prognostically predictive genes in a data set containing 251 NBs. Gene Ontology analysis was performed on significant genes with a positive hazard ratio to search for cellular processes associated with poor prognosis. An enrichment in ribonucleoproteins (RNPs) was found. Genes involved in the stabilization and formation of the central small nucleolar RNP (snoRNP) complex were scrutinized using a backward conditional Cox regression resulting in an snoRNP signature consisting of three genes: DKC1, NHP2, and GAR1. The snoRNP signature significantly and independently predicted prognosis when compared to the established clinical risk factors. Association of snoRNP protein expression and prognosis was confirmed using tissue microarrays. Knockdown of snoRNP expression in NB cell lines resulted in reduced telomerase activity and an increase in anaphase bridge frequency. In addition, in patient material, expression of the snoRNP complex was significantly associated with telomerase activity, occurrence of segmental aberrations, and expression-based measurements of chromosomal instability. Together, these results underscore the prognostic value of snoRNP complex expression in NB and suggest a role for snoRNPs in telomere maintenance and genomic stability. 相似文献
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Marta Perego 《PLoS biology》2013,11(3)
Signal transduction systems are influenced by positive and negative forces resulting in an output reflecting the sum of the opposing forces. The Rap family of regulatory protein modules control the output of two-component signal transduction systems through protein∶protein and protein∶peptide interactions. These modules and their peptide regulators are found in complex signaling pathways, including the bacterial developmental pathway to sporulation, competence, and protease secretion. Two articles published in the current issue of PLOS Biology reveal by means of crystallographic analyses how the Rap proteins of bacilli are regulated by their inhibitor Phr peptide and provide a mechanistic explanation for a genetic phenotype isolated decades earlier. The Rap-Phr module of bacterial regulators was the prototype of a family that now extends to other bacterial signaling proteins that involve the use of the tetratricopeptide repeat structural fold. The results invite speculation regarding the potential exploitation of this module as a molecular tool for applications in therapeutic design and biotechnology.Cell signaling by oligopeptides is a critical component of the biology of eukaryotic and prokaryotic cells. In microorganisms such as Gram-positive bacteria, small peptides have been found to regulate a variety of cellular functions, providing the bacteria with the ability to communicate and change behavior of the same or of other species in response to conditions and perturbations of the environment [1]. Studies in the spore-forming model organism Bacillus subtilis were among the first to identify pathways in which peptide signaling played a regulatory role. 相似文献
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Gwenaelle Gueguen Marta E. Kalamarz Johnny Ramroop Jeffrey Uribe Shubha Govind 《PLoS pathogens》2013,9(8)
Polydnaviruses are mutualists of their parasitoid wasps and express genes in immune cells of their Lepidopteran hosts. Polydnaviral genomes carry multiple copies of viral ankyrins or vankyrins. Vankyrin proteins are homologous to IκB proteins, but lack sequences for regulated degradation. We tested if Ichnoviral Vankyrins differentially impede Toll-NF-κB-dependent hematopoietic and immune signaling in a heterologous in vivo Drosophila, system. We first show that hematopoiesis and the cellular encapsulation response against parasitoid wasps are tightly-linked via NF-κB signaling. The niche, which neighbors the larval hematopoietic progenitors, responds to parasite infection. Drosophila NF-κB proteins are expressed in the niche, and non cell-autonomously influence fate choice in basal and parasite-activated hematopoiesis. These effects are blocked by the Vankyrin I2-vank-3, but not by P-vank-1, as is the expression of a NF-κB target transgene. I2-vank-3 and P-vank-1 differentially obstruct cellular and humoral inflammation. Additionally, their maternal expression weakens ventral embryonic patterning. We propose that selective perturbation of NF-κB-IκB interactions in natural hosts of parasitic wasps negatively impacts the outcome of hematopoietic and immune signaling and this immune deficit contributes to parasite survival and species success in nature. 相似文献