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Molecular Identification And Functional Characterization Of PIASy And SOCS1in Fish

Posted on:2012-01-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:R XiongFull Text:PDF
GTID:1110330371969163Subject:Cell biology
Abstract/Summary:PDF Full Text Request
This article is focused on the gene identification, induced expression pattern and biological function of PIASy and SOCS1in fishPIASy and SOCS1are members of two important families of negative regulators for the JAK-STAT signaling pathway. The two molecules are not specific to this pathway, but also participate in many other cytokine signaling pathways and the regulation of cell cycle, cell apoptosis, cell differentiation and immune responses.In the first part, based on the bioinformatics method such as homologous alignment analysis, we successfully identified and cloned the PIASy homologous gene from zebrafish. We analyzed the expression pattern of PIASy both at different embryonic development stages and in adult zebrafish tissues. The gene expression profilings of normal and poly(I:C) or recombinant IFNφ1-stimulated zebrafish were also detected. The high homology of amino acid sequences and conserved domains implied the conserved function of PIASy. PIASy functions as a negative regulator in a lot of signaling pathways in mammals, especially in immune related pathways. So we used zebrafish embryo as a model to study the role of zebrafish PIASy in TRIF, MAVS and IFN pathways, the results showed that this molecule could regulate all these pathways, which revealed the important roles of PIASy playing in the immune regulation of fish.In the second part, we analyzed the expression patterns of zebrafish SOCS1both at different embryonic development stages and in normal or poly (I:C)-stimulated adult tissues. The high homology of amino acid sequences and conserved domains indicated the conserved function of SOCS1in immune regulation of teleost fish. We used zebrafish embryo as a model to study the function of zebrafish SOCS1, and found that SOCS1could repress the IFN signaling pathway. We also analyzed the role of Tetraodon nigroviridis SOCS1(TnSOCS1) in Hela cells, found that TnSOCS1could regulate the human IFN-βsignaling pathway. These results suggested that fish SOCS1is a highly conserved molecule, which can play roles not only in teleost fish, but also in mammal cells, to repress the IFN pathway.
Keywords/Search Tags:fish, PIASy, SOCS1, TRIF, MAVS, IFN
PDF Full Text Request
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