THE DEAZAGUANINE-DERIVATIVE, QUEUINE, AFFECTS CELL-PROLIFERATION, PROTEIN-PHOSPHORYLATION AND THE EXPRESSION OF THE PROTO ONCOGENES C-FOS AND C-MYC IN HELA-CELLS

In higher eukaryotes the hypermodified guanine analogue, queuine (7-(5-(((1S,4S,5R)-4,5-dihydroxy-2-cyclopentene-1-yl)amino)-methyl)-7-deazaguanine), occurs free or as modified nucleoside (Q) in the anticodon of specific tRNAs. Fast proliferating tissues and tumors contain considerable amounts of free queuine and Q-deficient tRNAs. Here we show that HeLa cells can be grown in the absence or presence of queuine. In response to queuine, and under appropriate conditions, (i) the proliferation of HeLa cells was stimulated, (ii) the steady-state level of c-fos mRNA was reduced, contrary that of c-myc mRNA was elevated, and (iii) in cytosolic extracts protein phosphorylation especially for a 42 kDa protein was significantly increased. The results suggest that queuine substitutes for growth factors in a signal transduction pathway. © 1990.