Mitogenic stimulation of HeLa cells increases the activity of the anoxic stress protein, LDH 6/k: suppression by queuine.

Mitogenic stimulation of quiescent mammalian cells triggers an array of early events crucial for cell cycle progression. Here we show that the activity of the anoxic stress protein, lactate dehydrogenase 6/k, transiently increased after mitogenic stimulation of serum-starved HeLa cells. Regulation of lactate dehydrogenase 6/k activity in early G1 depended on the activity of a receptor tyrosine kinase and on protein and mRNA synthesis, but did not involve protein kinase C. The guanine analog, queuine, an ubiquitously occurring tRNA base of bacterial origin, suppressed the mitogen-induced protein synthesis and also the transient increase in lactate dehydrogenase 6/k activity. The results suggest that queuine relieves hypoxic stress resulting from mitogenic stimulation by suppressing protein synthesis during G0/G1 transition.