Control of cell-cycle-associated tetrahydrobiopterin synthesis in rat thymocytes.
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.
Schott
K
K
GSF-Forschungszentrum für Umwelt und Gesundheit, GmbH, Institut für Experimentelle Hämatologie, München.
Brand
K
K
Hatakeyama
K
K
Kagamiyama
H
H
Maier
J
J
Werner
T
T
Ziegler
I
I
D000429:Alcohol Oxidoreductases / Q000032:analysis; D000818:Animals; D001483:Base Sequence; D001708:Biopterins / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D002453:Cell Cycle; D002478:Cells, Cultured / Q000378:metabolism; D015342:DNA Probes; D005260:Female; D006136:GTP Cyclohydrolase / Q000032:analysis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000378:metabolism*
D015342:DNA Probes; D012333:RNA, Messenger; D001708:Biopterins; D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase; D006136:GTP Cyclohydrolase; C003402:sapropterin