Control of 5',5'-dinucleoside triphosphate catabolism by APH1, a Saccharomyces cerevisiae analog of human FHIT.
The putative human tumor suppressor gene FHIT (fragile histidine triad) (M. Ohta et al., Cell 84:587-597, 1996) encodes a protein behaving in vitro as a dinucleoside 5',5"'-P1,P3-triphosphate (Ap3A) hydrolase. In this report, we show that the Saccharomyces cerevisiae APH1 gene product, which resembles human Fhit protein, also hydrolyzes dinucleoside 5',5'-polyphosphates, with Ap3A being the preferred substrate. Accordingly, disruption of the APH1 gene produced viable S. cerevisiae cells containing reduced Ap3A-hydrolyzing activity and a 30-fold-elevated Ap3N concentration.
Chen
J
J
Laboratoire de Biochimie, URA 1970 CNRS, Ecole Polytechnique, Palaiseau, France.
Brevet
A
A
Blanquet
S
S
Plateau
P
P
D017766:Acid Anhydride Hydrolases; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D016296:Mutagenesis; D009363:Neoplasm Proteins; D010727:Phosphoric Diester Hydrolases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011506:Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D013045:Species Specificity; D013379:Substrate Specificity; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D015226:Dinucleoside Phosphates; D009363:Neoplasm Proteins; D010727:Phosphoric Diester Hydrolases; D011506:Proteins; D011994:Recombinant Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C020023:bis(5'-nucleosyl)tetraphosphatase (asymmetrical)