Control of cell-cycle-associated tetrahydrobiopterin synthesis in rat thymocytes. |
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Authors: | K Schott K Brand K Hatakeyama H Kagamiyama J Maier T Werner I Ziegler |
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Affiliation: | GSF-Forschungszentrum für Umwelt und Gesundheit, GmbH, Institut für Experimentelle H?matologie, München. |
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Abstract: | The cell-cycle progression of rat thymocytes from G0 through G1 to DNA synthesis is associated with a transient synthesis of H4biopterin, the concentration of which reaches a maximum at the time of S-phase entry and then decreases. This synthesis of H4biopterin is controlled by the specific activity of GTP cyclohydrolase I, which peaks in G1/S cells. In contrast, the catalytic activity of sepiapterin reductase remains constant throughout the cell-cycle. At G0 the steady state mRNA levels specific for GTP cyclohydrolase I and sepiapterin reductase, respectively, are below the limits of detection. Both accumulate as the thymocytes progress through the cell-cycle but lack cyclic down regulation. The data indicate that the variations in H4biopterin synthesis during the cell-cycle are caused by growth regulated increase in GTP cyclohydrolase I mRNA expression, with subsequent post-translational inactivation. This latter is likely due to the degree of enzyme phosphorylation. |
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