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  • 1
    Digitale Medien
    Digitale Medien
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 67 (1997), S. 24-31 
    ISSN: 0730-2312
    Schlagwort(e): growth control ; transcription ; repression ; dihydrofolate reductase ; retinoblastoma ; Balb/c 3T3 cells ; TATAA-less promoter ; gene expression ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Dihydrofolate reductase activity is required for many biosynthetic pathways including nucleotide synthesis. Its expression is therefore central to cellular growth, and it has become a key target for cancer chemotherapy. Transcription of the dihydrofolate reductase gene is regulated with growth, being expressed maximally in late G1/early S phase following serum stimulation of quiescent cells. This regulation is directed by a promoter which contains binding sites for only the transcription factors Sp1 and E2F. In this study, the role of these promoter elements in growth/cell cycle regulation of dihydrofolate transcription was addressed directly by transient transfection of Balb/c 3T3 cells with mutant promoter-reporter gene constructs. The E2F sites were found to repress transcription in G0 and early G1 but did not contribute to the level of transcription in late G1/S phase. In contrast, Sp1 sites were able to mediate induction of transcription from the dihydrofolate reductase promoter, as well as a heterologous promoter, following serum stimulation of quiescent cells. These findings add dihydrofolate reductase to a growing list of genes at which E2F sites are primarily repressive elements and delineate a role for Sp1 sites in the growth/cell cycle regulation of transcription. J. Cell. Biochem. 67: 24-31, 1997. © 1997 Wiley-Liss, Inc.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 138 (1989), S. 439-449 
    ISSN: 0021-9541
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Medizin
    Notizen: Although acquired thermotolerance has been linked to the induction of heat shock proteins, the molecular mechanism(s) by which cells become resistant to heat is unknown. The present study shows a strong correlation between the survival of cells following heat shock and the rate of recovery of protein, total KNA, and rRNA synthesis. Increasing exposure of CHO cells to 45°C was found to decrease survival and cause a lengthening delay in these synthetic processes. The same reciprocal correlation was seen in thermotolerant cells. As thermotol-erance develops, more cells survive a heat challenge and the delay in synthesis decreases. These data argue that enhanced recovery of protein and RNA synthesis is one factor which plays a key role in thermotolerance.The involvement of rRNA synthesis was further investigated by using actinomy-cin D at 0.1 μg ml-1, a concentration at which rRNA synthesis is selectively inhibited. When the drug was present during the recovery from a challenge heat treatment, the survival of thermotolerant cells was 3-fold lower than expected from the mild toxicity of the drug. As this could not be accounted for by an interaction of the drug with the response of cells to single heat treatments, it is concluded that the drug inhibits the expression of thermotolerance in cells which would otherwise express a full degree of thermotolerance. The time and concentration dependence of this effect indicates that the drug acts though inhibition of rRNA synthesis. Therefore, enhanced recovery of RNA synthesis, presumably rRNA synthesis, is identified as one of the mechanisms responsible for enhanced survival of thermotolerant cell following heat shock.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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