Transforming Growth Factor β1 Inhibition of p34^cdc2 Phosphorylation and Histone H1 Kinase Activity Is Associated with G1/S-Phase Growth Arrest

Abstract

Transforming growth factor β1 (TGFβ1) is a potent inhibitor of epithelial cell proliferation. We present data which indicate that epithelial cell proliferation is inhibited when TGFβ1 is added throughout the prereplicative G1 phase. Cultures become reversibly blocked in late G1 at the G1/S-phase boundary. The inhibitory effects of TGFβ1 on cell growth occur in the presence of the RNA synthesis inhibitor 5,6-dichloro-1-β-D-ribofurano- sylbenzimidazole. Associated with this inhibitory effect is a decrease in the phosphorylation and histone H1 kinase activity of the p34^cdc2 protein kinase. These data suggest that TGFβ1 growth inhibition in epithelial cells involves the regulation of p34^cdc2 activity at the G1/S transition.