Growth inhibition by TGF-β linked to suppression of retinoblastoma protein phosphorylation
M Laiho, JA DeCaprio, JW Ludlow, DM Livingston… - Cell, 1990 - cell.com
M Laiho, JA DeCaprio, JW Ludlow, DM Livingston, J Massague
Cell, 1990•cell.comThe growth-suppressive function of the retinoblastoma gene product, RB, has been ascribed
to the underphosphorylated RB form that prevails during Gl phase in the cell cycle. We show
that addition of the paracrine growth inhibitor transforming growth factor f31 (TGF-pl) to
MvlLu lung epithelial cells in mid to late Gl prevents phosphorylation of RB scheduled for
this cell cycle stage and arrests cells in late Gl. Expression of SV40 T antigen, a transforming
protein that binds underphosphorylated FIB, does not block the effect of TGF-pl on RB …
to the underphosphorylated RB form that prevails during Gl phase in the cell cycle. We show
that addition of the paracrine growth inhibitor transforming growth factor f31 (TGF-pl) to
MvlLu lung epithelial cells in mid to late Gl prevents phosphorylation of RB scheduled for
this cell cycle stage and arrests cells in late Gl. Expression of SV40 T antigen, a transforming
protein that binds underphosphorylated FIB, does not block the effect of TGF-pl on RB …
Summary
The growth-suppressive function of the retinoblastoma gene product, RB, has been ascribed to the underphosphorylated RB form that prevails during Gl phase in the cell cycle. We show that addition of the paracrine growth inhibitor transforming growth factor f31 (TGF-pl) to MvlLu lung epithelial cells in mid to late Gl prevents phosphorylation of RB scheduled for this cell cycle stage and arrests cells in late Gl. Expression of SV40 T antigen, a transforming protein that binds underphosphorylated FIB, does not block the effect of TGF-pl on RB phosphorylation but greatly reduces the growth-inhibitory response to TGFj31. TGF-pl and RB appear to function in a common growth-inhibitory pathway in which TGF-fll acts to retain RB in the underphosphorylated, growth-suppressive state.
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