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Pathway Proteins (pathway + protein)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

A transcriptomic and proteomic analysis of the effect of CpG-ODN on human THP-1 monocytic leukemia cells

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2005
Cheng-Chin Kuo
Abstract The CpG motif of bacterial DNA (CpG-DNA) is a potent immunostimulating agent whose mechanism of action is not yet clear. Here, we used both DNA microarray and proteomic approaches to investigate the effects of oligodeoxynucleotides containing the CpG motif (CpG-ODN) on gene transcription and protein expression profiles of CpG-ODN responsive THP-1 cells. Microarray analysis revealed that 2,h stimulation with CpG-ODN up-regulated 50,genes and down-regulated five genes. These genes were identified as being associated with inflammation, antimicrobial defense, transcriptional regulation, signal transduction, tumor progression, cell differentiation, proteolysis and metabolism. Longer stimulation (8,h) with CpG-ODN enhanced transcriptional expression of 58,genes. Among these 58,genes, none except one, namely WNTI inducible signaling pathway protein,2, was the same as those induced after 2,h stimulation. Proteomic analysis by two-dimensional gel electrophoresis, followed by mass spectrometry identified several proteins up-regulated by CpG-ODN. These proteins included heat shock proteins, modulators of inflammation, metabolic proteins and energy pathway proteins. Comparison of microarray and proteomic expression profiles showed poor correlation. Use of more reliable and sensitive analyses, such as reverse transcriptase polymerase chain reaction, Western blotting and functional assays, on several genes and proteins, nonetheless, confirmed that there is indeed good correlation between mRNA and protein expression after CpG-ODN treatment. This study also revealed that several anti-apoptotic and neuroprotective related proteins, not previously reported, are activated by CpG-DNA. These findings have extended our knowledge on the activation of cells by CpG-DNA and may contribute to further understanding of mechanisms that link innate immunity with acquired immune response(s). [source]

Targeted therapy in inflammatory breast cancer,

CANCER, Issue S11 2010
Hideko Yamauchi MD
Abstract Despite the introduction of multimodality treatment approaches, the prognosis of inflammatory breast cancer (IBC) is poor. Recent developments in molecular targeted therapy may be effective against IBC. The authors report the results of a literature review. Trastuzumab and lapatinib, which target human epidermal growth factor receptor 2 (HER-2), have demonstrated benefit in clinical trials for HER-2,positive breast cancers. WNT1-inducible signaling pathway protein 3, Ras homolog gene family member C guanosine triphosphatase, epidermal growth factor receptor (EGFR), and p27kip1 also have been studied as potential targets in IBC. Molecular targets in vasculolymphatic processes (angiogenesis, lymphangiogenesis, and vasculogenesis) have demonstrated greater potential in IBC than in non-IBC. Although loss of E-cadherin is a hallmark of epithelial-to-mesenchymal transition and may correlate with the promotion of metastasis, paradoxically, E-cadherin is overexpressed in IBC through an unknown mechanism. On the basis of dissecting the molecular mechanism of the aggressiveness of IBC, the authors currently are investigating whether EGFR may aid in developing innovative targeted therapies. Cancer 2010;116(11 suppl):2758,9. © 2010 American Cancer Society. [source]

Novel alternatively spliced endoplasmic reticulum retention signal in the cytoplasmic loop of Proteolipid Protein-1

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2007
Cherie Southwood
Abstract Increased awareness about the importance of protein folding and trafficking to the etiology of gain-of-function diseases has driven extensive efforts to understand the cell and molecular biology underlying the life cycle of normal secretory pathway proteins and the detrimental effects of abnormal proteins. In this regard, the quality-control machinery in the endoplasmic reticulum (ER) has emerged as a major mechanism by which cells ensure that secreted and transmembrane proteins either adopt stable secondary, tertiary, and quaternary structures or are retained in the ER and degraded. Here we examine cellular and molecular aspects of ER retention in transfected fibroblasts expressing missense mutations in the Proteolipid Protein-1 (PLP1) gene that cause mild or severe forms of neurodegenerative disease in humans. Mild mutations cause protein retention in the ER that is partially dependent on the presence of a cytoplasmically exposed heptapeptide, KGRGSRG. In contrast, retention associated with severe mutations occurs independently of this peptide. Accordingly, the function of this novel heptapeptide has a significant impact on pathogenesis and provides new insight into the functions of the two splice isoforms encoded by the PLP1 gene, PLP1 and DM-20. © 2006 Wiley-Liss, Inc. [source]

A transcriptomic and proteomic analysis of the effect of CpG-ODN on human THP-1 monocytic leukemia cells

Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy

ANNALS OF NEUROLOGY, Issue 1 2010
Mohammad Salajegheh MD
Objective We investigated interferon-stimulated gene 15 (ISG15), a poorly understood ubiquitin-like modifier, and its enzymatic pathway in dermatomyositis (DM), an autoimmune disease primarily involving muscle and skin. Methods We generated microarray data measuring transcript abundance for approximately 18,000 genes in each of 113 human muscle biopsy specimens, and studied biopsy specimens and cultured skeletal muscle using immunohistochemistry, immunoblotting proteomics, real-time quantitative polymerase chain reaction, and laser-capture microdissection. Results Transcripts encoding ISG15-conjugation pathway proteins were markedly upregulated in DM with perifascicular atrophy (DM-PFA) muscle (ISG15 339-fold, HERC5 62-fold, and USP18 68-fold) compared with 99 non-DM samples. Combined analysis with publicly available microarray datasets showed that >50-fold ISG15 transcript elevation had 100% sensitivity and specificity for 28 biopsies from adult DM-PFA and juvenile DM patients compared with 199 muscle samples from other muscle diseases. Free ISG15 and ISG15-conjugated proteins were only found on immunoblots from DM-PFA muscle. Cultured human skeletal muscle exposed to type 1 interferons produced similar transcripts and ISG15 protein and conjugates. Laser-capture microdissection followed by proteomic analysis showed deficiency of titin in DM perifascicular atrophic myofibers. Interpretation A large-scale microarray study of muscle samples demonstrated that among a diverse group of muscle diseases DM was uniquely associated with upregulation of the ISG15 conjugation pathway. Exposure of human skeletal muscle cell culture to type 1 interferons produced a molecular picture highly similar to that seen in human DM muscle. Perifascicular atrophic myofibers in DM were deficient in a number of skeletal muscle proteins including titin. ANN NEUROL 2010;67:53,63 [source]

Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: Prominent role of Wnt-induced signaling protein 1

ARTHRITIS & RHEUMATISM, Issue 2 2009
Arjen B. Blom
Objective Wnt signaling pathway proteins are involved in embryonic development of cartilage and bone, and, interestingly, developmental processes appear to be recapitulated in osteoarthritic (OA) cartilage. The present study was undertaken to characterize the expression pattern of Wnt and Fz genes during experimental OA and to determine the function of selected genes in experimental and human OA. Methods Longitudinal expression analysis was performed in 2 models of OA. Levels of messenger RNA for genes from the Wnt/,-catenin pathway were determined in synovium and cartilage, and the results were validated using immunohistochemistry. Effects of selected genes were assessed in vitro using recombinant protein, and in vivo by adenoviral overexpression. Results Wnt-induced signaling protein 1 (WISP-1) expression was strongly increased in the synovium and cartilage of mice with experimental OA. Wnt-16 and Wnt-2B were also markedly up-regulated during the course of disease. Interestingly, increased WISP-1 expression was also found in human OA cartilage and synovium. Stimulation of macrophages and chondrocytes with recombinant WISP-1 resulted in interleukin-1,independent induction of several matrix metalloproteinases (MMPs) and aggrecanase. Adenoviral overexpression of WISP-1 in murine knee joints induced MMP and aggrecanase expression and resulted in cartilage damage. Conclusion This study included a comprehensive characterization of Wnt and Frizzled gene expression in experimental and human OA articular joint tissue. The data demonstrate, for the first time, that WISP-1 expression is a feature of experimental and human OA and that WISP-1 regulates chondrocyte and macrophage MMP and aggrecanase expression and is capable of inducing articular cartilage damage in models of OA. [source]