The Fhit tumor suppressor protein regulates the intracellular concentration of diadenosine triphosphate but not diadenosine tetraphosphate.
To determine the role of the FHIT tumor suppressor gene product, a diadenosine 5',5'''-P1,P3-triphosphate (Ap3A) hydrolase, in the regulation of the concentration of Ap3A and diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) in vivo, the levels of the adenosine(5')triphospho(5')nucleoside (Ap3N) and adenosine(5')tetraphospho(5')nucleoside (Ap4N) families were measured by luminometry in a number of human cell lines and correlated with the expression of Fhit determined by immunoblotting. Fhit-positive cells had no Ap3N or a very low level of Ap3N, whereas most Fhit-negative cells had Ap3N in the range 0.2-0.9 pmol/10(6) cells. Ap4N (mean value, 0.17 pmol/10(6) cells) did not correlate with Fhit expression. The results suggest that Fhit efficiently metabolizes Ap3A and Ap3N but not Ap4A or Ap4N in vivo.
Murphy
G A
GA
Cell Regulation and Signalling Group, School of Biological Sciences, University of Liverpool, United Kingdom.
Halliday
D
D
McLennan
A G
AG
D017766:Acid Anhydride Hydrolases; D015153:Blotting, Western; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D009363:Neoplasm Proteins / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D015226:Dinucleoside Phosphates; D009363:Neoplasm Proteins; D011506:Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate