Transcription Factor Binding Motifs, Chromosome mapping and Gene Ontology analysis in Cross-platform microarray data from bladder cancer.

<p>We have previously analyzed the gene expression profile in urinary bladder cancer and determined the differentially expressed (DE) genes between cancer and healthy tissue. We aimed: 1) To identify the over-represented Transcription Factor Binding Motifs (TFBMs) in the promoters of the DE genes. 2) To map the DE genes on the chromosomal regions. 3) To gain more insight into the DE gene functions, using Gene Ontology (GO) analysis. We investigated the TFBMs in the Transcription Element Listening System Database (TELiS). The TRANSFAC TF database was used for the identification of TF binding sites. The Gene Ontology Tree Machine, WebGestalt web-tool and the Matlab ® (The Mathworks Inc.) computing environments were used for chromosome mapping. GO analysis was performed using the eGOn online tool. The WebGestalt web-tool was used for gene function classifications. Relations of the DE genes and the transcription factor binding motifs were further investigated using the Pubgene Ontology Database. The glucocorticoid receptor (GR) was predicted as one of the TFs in the common gene set. In order to find which gene was most commonly represented among the TFs, we plotted the incidence of each gene as a function of the times of appearance within the predicted TFs. The gene BMP4 (bone morphogenetic protein 4; ID: 652) exhibited the higher number of binding sites for the predicted TFs. The majority of the chromosomes in BC had inactivated (down-regulated) genes, compared to the normal tissue. However, two genes were significantly over-expressed: CDC20 (in chromosome 1) and HCCS (in chromosome X). Three main functions were outlined by GO for the DE genes: a) circulatory system regulation, b) reproductive organ and sex development, and c) catecholamine metabolism. This enrichment showed that the predicted gene set has more than a dual role. Through this study, we were able to identify several important factors that warrant further investigation both as prognostic markers and as therapeutic targets for bladder cancer. Such approaches may provide a better insight into tumorigenesis and tumor progression.</p

RhoB is a component of the human cytomegalovirus assembly complex and is required for efficient viral production

<p>Human Cytomegalovirus (HCMV), an ubiquitous β-herpesvirus, is a significant pathogen that causes medically severe diseases in immunocompromised individuals and in congenitally infected neonates. RhoB belongs to the family of Rho GTPases, which regulates diverse cellular processes. Rho proteins are implicated in the entry and egress from the host cell of mainly α- and γ-herpesviruses, whereas β-herpesviruses are the least studied in this regard. Here, we studied the role of RhoB GTPase during HCMV lytic infection. Microscopy analysis, both in fixed and live infected cells showed that RhoB was translocated to the assembly complex/compartment (AC) of HCMV, a cytoplasmic zone in infected cells where many viral structural proteins are known to accumulate and assembly of new virions takes place. Furthermore, RhoB was localized at the AC even when the expression of the late HCMV AC proteins was inhibited. At the very late stages of infection, cellular projections were formed containing RhoB and HCMV virions, potentially contributing to the successful viral spread. Interestingly, the knockdown of RhoB in HCMV-infected cells resulted in a significant reduction of the virus titer and could also affect the accumulation of AC viral proteins at this subcellular compartment. RhoB knockdown also affected actin fibers' structure. Actin reorganization was observed at late stages of infection originating from the viral AC and surrounding the cellular projections, implying a potential interplay between RhoB and actin during HCMV assembly and egress. In conclusion, our results demonstrate for the first time that RhoB is a constituent of the viral AC and is required for HCMV productive infection.</p