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Database Mining (database + mining)
Selected AbstractsEndothelial cell-specific molecule 2 (ECSM2) modulates actin remodeling and epidermal growth factor receptor signalingGENES TO CELLS, Issue 3 2009Fanxin Ma Endothelial cell-specific molecules (ECSMs) play a pivotal role in the pathogenesis of many angiogenesis-related diseases. Since its initial discovery, the exact function of human ECSM2 has not been defined. In this study, by database mining, we identified a number of hypothetical proteins across species exhibiting substantial sequence homology to the human ECSM2. We showed that ECSM2 is preferentially expressed in endothelial cells and blood vessels. Their characteristic structures and unique expression patterns suggest that ECSM2 is an evolutionarily conserved gene and may have important functions. We further explored the potential roles of human ECSM2 at the molecular and cellular level. Using a reconstitution mammalian cell system, we demonstrated that ECSM2 mainly resides at the cell membrane, is critically involved in cell-shape changes and actin cytoskeletal rearrangement, and suppresses tyrosine phosphorylation signaling. More importantly, we uncovered that ECSM2 can cross-talk with epidermal growth factor receptor (EGFR) to attenuate the EGF-induced cell migration, possibly via inhibiting the Shc-Ras-ERK (MAP kinase) pathway. Given the importance of growth factor and receptor tyrosine kinase-mediated signaling and cell migration in angiogenesis-related diseases, our findings regarding the inhibitory effects of ECSM2 on EGF-mediated signaling and cell motility may have important therapeutic implications. [source] High throughput functional genomics: Identification of novel genes with tumor suppressor phenotypesINTERNATIONAL JOURNAL OF CANCER, Issue 3 2005Kerstin Koenig-Hoffmann Abstract We have used a combination of high throughput functional genomics, computerized database mining and expression analyses to discover novel human tumor suppressor genes (TSGs). A genome-wide high throughput cDNA phenotype screen was established to identify genes that induce apoptosis or reduce cell viability. TSGs are expressed in normal tissue and frequently act by reduction of growth of transformed cells or induce apoptosis. In agreement with that and thus serving as platform validation, our pro-apoptotic hits included genes for which tumor suppressing activities were known, such as kangai1 and CD81 antigen. Additional genes that so far have been claimed as putative TSGs or associated with tumor inhibitory activities (prostate differentiation factor, hRAS-like suppressor 3, DPH2L1-like and the metastasis inhibitor Kiss1) were confirmed in their proposed TSG-like phenotype by functionally defining their growth inhibitory or pro-apoptotic function towards cancer cells. Finally, novel genes were identified for which neither association with cell growth nor with apoptosis were previously described. A subset of these genes show characteristics of TSGs because they (i) reduce the growth or induce apoptosis in tumor cells; (ii) show reduced expression in tumor vs. normal tissue; and (iii) are located on chromosomal (LOH-) loci for which cancer-associated deletions are described. The pro-apoptotic phenotype and differential expression of these genes in normal and malignant tissue make them promising target candidates for the diagnosis and therapy of various tumors. [source] Preparing undergraduates to participate in the post-genome era: A capstone laboratory experience in proteomics,BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION, Issue 6 2003Eric S. Eberhardt Abstract Proteomics is one of the important new disciplines to emerge from the genome sequencing projects of the last decade. In order to introduce our students to the techniques and promise of this emerging field, a capstone laboratory experience has been developed. The exercise involves multiple aspects of proteomics research including microbial culturing methods, two-dimensional gel electrophoresis techniques, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, and database mining. Over a 12-week semester, students design their own experiments and apply a proteomic approach to investigate the heat shock response in Escherichia coli. In the trial presented in this article, students successfully identified several major heat shock proteins. The laboratory outlined here can be readily adapted to explore a wide variety of responses in metabolic pathways or responses resulting from other environmental insults or stresses. Additionally, the laboratory can be modified to explore the proteomes of organelles, tissues, and other model organisms. [source] RNA interference in protozoan parasitesCELLULAR MICROBIOLOGY, Issue 6 2004Elisabetta Ullu Summary RNA interference or RNAi is defined as the mechanism through which gene-specific, double-stranded RNA (dsRNA) triggers degradation of homologous transcripts. Besides providing an invaluable tool to downregulate gene expression in a variety of organisms, it is now evident that RNAi extends its tentacles into both the nucleus and the cytoplasm and is involved in a variety of gene silencing phenomena. Here we review the current status of RNAi in protozoan parasites that cause diseases of considerable medical and veterinary importance throughout Africa, Asia and the Americas. RNAi was first discovered in Trypanosoma brucei, a species of the family Trypanosomatidae, and it rapidly became the method of choice to downregulate gene expression in these organisms. At the same time, mechanistic studies exposed a role for RNAi in the control of retroposon transcript abundance. Whereas RNAi is also present in T. congolense, other members of the same family of organisms, namely T. cruzi and Leishmania major, are RNAi-negative. In apicomplexan parasites, there is experimental evidence for RNAi in Plasmodium, but this is not supported by their genetic make up. In contrast, the genome of Toxoplasma gondii harbours gene candidates with convincing similarity to ,classical' RNAi genes. Thus, as previously shown in fungi, protozoan parasites are genetically heterogeneous as far as the RNAi pathway is concerned. Finally, database mining predicts that Entamoeba histolytica and Giardia intestinalis have an RNAi pathway and the presence of RNAi genes in Giardia supports the view that gene silencing by dsRNA appeared very early during evolution of the eukaryotic lineage. [source] | ||||||||||