TRANSFORMING GROWTH FACTOR-BETA-1 INHIBITION OF P34CDC2 PHOSPHORYLATION AND HISTONE-H1 KINASE-ACTIVITY IS ASSOCIATED WITH G1/S-PHASE GROWTH ARREST

Transforming growth factor beta-1 (TGF-beta-1) is a potent inhibitor of epithelial cell proliferation. We present data which indicate that epithelial cell proliferation is inhibited when TGF-beta-1 is added throughout the prereplicative G1 phase. Cultures become reversibly blocked in late G1 at the G1/S-phase boundary. The inhibitory effects of TGF-beta-1 on cell growth occur in the presence of the RNA synthesis inhibitor 5,6-dichloro-1-beta-D-ribofurano-sylbenzimidazole. Associated with this inhibitory effect is a decrease in the phosphorylation and histone H1 kinase activity of the p34cdc2 protein kinase. These data suggest that TGF-beta-1 growth inhibition in epithelial cells involves the regulation of p34cdc2 activity at the G1/S transition.