Regulation of nuclear factors in the interleukin-6 signaling pathway.
Item
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Title
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Regulation of nuclear factors in the interleukin-6 signaling pathway.
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Identifier
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AAI9431368
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identifier
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9431368
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Creator
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Hsu, Wei.
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Contributor
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Adviser: Selina Chen-Kiang
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Date
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1994
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular | Biology, Cell | Biology, Microbiology
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Abstract
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Regulation of nuclear factors in response to interleukin-6 (IL-6) has been investigated in order to understand the molecular mechanism underlying IL-6 signaling. Members of the NF-IL6 and AP-1 families, which share the common basic leucine zipper structure, are thought to mediate the nuclear signals of IL-6. The functional and physical interactions between NF-IL6 and AP-1 family proteins in vitro and in vivo have been demonstrated. The direct associations of NF-IL6 and AP-1 are independent of their DNA recognition elements. These associations lead to modifications of the DNA-binding specificity and transcriptional activity of NF-IL6 and AP-1 family proteins. Although the leucine zipper domain is necessary and sufficient to mediate the cross-family dimerization, regions outside the basic leucine zipper structure can enhance the binding of NF-IL6-Fos complexes to specific DNA sequences in the electrophoretic mobility shift assay. The coordinate elevations of NF-IL6 and Jun by IL-6 trigger their association upon macrophage differentiation. Regulated associations of these two family proteins may have implications for determining the promoter specific transcription by IL-6 induction. The octamer binding proteins are regulated by IL-6 suggesting that they represent a subset of DNA-binding proteins that respond to IL-6 signals. OCT-1 is downstream of NF-IL6 in the nuclear signaling cascade induced by IL-6. The abundance of OCT-1 and the ratio of NF-IL6 isoforms are convergently regulated by two diverse signals, IL-6 and retinoic acid. The enhanced synthesis of NF-IL6 and OCT-1 correlates with one of their functions: the stimulation of adenovirus DNA replication. This result provides an example of possible functional consequences of IL-6 and retinoic acid signaling mediated through the regulation of NF-IL6 and OCT-1. Studies presented in this thesis contribute to understanding of the mechanism underlying the IL-6 signal transduction pathway, the IL-6 inducible transcription and the pleiotropic effect of IL-6.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
