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-ribofuranosylbenzimidazole. 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.
Howe
P H
PH
Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232.
Draetta
G
G
Leof
E B
EB
D000818:Animals; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006131:Growth Inhibitors; D006657:Histones / Q000378:metabolism; D008907:Mink; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D006131:Growth Inhibitors; D006657:Histones; D010750:Phosphoproteins; D016212:Transforming Growth Factor beta; D004004:Dichlororibofuranosylbenzimidazole; D016203:CDC2 Protein Kinase; D012319:RNA Polymerase II