The Synthesis of Acidic Nuclear Proteins in the Prereplicative Phase of the Isoproterenol-stimulated Salivary Gland

A single injection of isoproterenol results, after a lag period of 20 hours, in a marked stimulation of DNA synthesis and cell proliferation in the mouse salivary gland. The incorporation of leucine-3H into three acidic nuclear protein fractions (nonhistone nuclear proteins) increases within 30 min following the administration of isoproterenol and does not return to control levels until 48 hours later. The three fractions consist of (a) a fraction soluble in Tris-EDTA (ribonucleoprotein fraction); (b) one extractable from nuclei with 0.15 n NaCl; and (c) an acidic fraction insoluble in the above solutions and in 0.25 n H2SO4 (residual fraction). The incorporation of leucine-3H into acidic nuclear proteins reaches its peak 12 hours after isoproterenol injection while the peak activity of the histone fraction coincides with the peak of DNA synthesis. Since the specific activity of the leucine pool does not change in stimulated glands, the increased incorporation of leucine-3H into acidic nuclear proteins indicates an increase in the rate of synthesis of these proteins. Actinomycin D given 30 min prior to isoproterenol inhibits isoproterenol-stimulated DNA synthesis but does not affect the increase in the rate of synthesis of nuclear proteins which occurs 2 hours after isoproterenol. However, the increases in the rates of synthesis occurring at 8 and 12 hours are inhibited. Cycloheximide, administered 1 hour after isoproterenol, inhibits isoproterenol-stimulated DNA synthesis as well as the increase in acidic nuclear protein synthesis at 8 and 12 hours. These results indicate a temporal difference in the synthesis of histones and acidic proteins during the transition of G0 cells to the S phase and suggest that acidic nuclear proteins may be involved in the control of cell proliferation in mammalian cells.