NF-IL6 is a cellular homologue for adenovirus E1A proteins.
Item
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Title
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NF-IL6 is a cellular homologue for adenovirus E1A proteins.
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Identifier
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AAI9224859
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identifier
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9224859
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Creator
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Spergel, Jonathan Michael.
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Contributor
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Adviser: Selina Chen-Kiang
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Date
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1992
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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, Microbiology
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Abstract
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The products of adenovirus E1A gene are transcription activators and repressors. Despite intense efforts, the molecular mechanism of E1A action remains to be elucidated. The complexity of delineating the mechanism of E1A action is compounded by the fact that it induces some promoters and not others, without apparent sequence specificity. A cellular activity (or activities) which functionally substitutes for E1A in transactivating an E1A-responsive adenovirus promoter has previously been shown to be present in embryonal carcinoma cells, in mouse oocytes, and during early development in preimplantation embryos. Its identity, however, has remained obscure. I have found a functionally related E1A-substituting cellular activity in HepG2 cells, of a human hepatoblastoma cell line. The E1A-responsive adenoviral promoters were active in HepG2 cells in the absence of E1A, when assayed by either transfection or viral infection. Furthermore, HepG2 cells supported productive infection of E1A-deletion mutant virus. The E1A-substituting activity in HepG2 cells increases dramatically upon induction by the cytokine interleukin-6, unlike the activity present in embryonal carcinoma cells, which diminishes upon cellular differentiation.;The enhancement of the E1A-substituting activity in HepG2 cells by IL-6 suggests that a nuclear factor(s) regulated by or transducing the IL-6 signal may mediate, or in itself be, the cellular activity which functionally substitutes for E1A. Towards this end, I have found that NF-IL6, an IL-6 regulated transcription factor, can regulate E1A-responsive genes in the absence of E1A. It functions as a positive or negative regulator for the E1A-responsive E2ae promoter in a concentration-dependent manner via NF-IL6 recognition sequences. These results suggest that there is an overlap of signal transduction pathways elicited by the transforming gene E1A and by the cytokine IL-6. These results also represent the first demonstration of a defined cellular factor which substitutes for E1A.
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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.
