Growth inhibition by TGF-β linked to suppression of retinoblastoma protein phosphorylation

Marikki Laiho; James A. DeCaprio; John W. Ludlow; David M. Livingston; Joan Massague

doi:10.1016/0092-8674(90)90251-9

Growth inhibition by TGF-β linked to suppression of retinoblastoma protein phosphorylation

Marikki Laiho, James A. DeCaprio, John W. Ludlow, David M. Livingston, Joan Massague

Research output: Contribution to journal › Article › peer-review

657 Scopus citations

Abstract

The growth-suppressive function of the retinoblastoma gene product, RB, has been ascribed to the underphosphorylated RB form that prevails during G1 phase in the cell cycle. We show that addition of the paracrine growth inhibitor transforming growth factor β1 (TGF-β1) to Mv1Lu lung epithelial cells in mid to late G1 prevents phosphorylation of RB scheduled for this cell cycle stage and arrests cells in late G1. Expression of SV40 T antigen, a transforming protein that binds underphosphorylated RB, does not block the effect of TGF-β1 on RB phosphorylation but greatly reduces the growth-inhibitory response to TGF-β1. TGF-β1 and RB appear to function in a common growth-inhibitory pathway in which TGF-β1 acts to retain RB in the underphosphorylated, growth-suppressive state.

Original language	English (US)
Pages (from-to)	175-185
Number of pages	11
Journal	Cell
Volume	62
Issue number	1
DOIs	https://doi.org/10.1016/0092-8674(90)90251-9
State	Published - Jul 13 1990
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/0092-8674(90)90251-9

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@article{385567e19ac5473385b34a93ad0a8fda,

title = "Growth inhibition by TGF-β linked to suppression of retinoblastoma protein phosphorylation",

abstract = "The growth-suppressive function of the retinoblastoma gene product, RB, has been ascribed to the underphosphorylated RB form that prevails during G1 phase in the cell cycle. We show that addition of the paracrine growth inhibitor transforming growth factor β1 (TGF-β1) to Mv1Lu lung epithelial cells in mid to late G1 prevents phosphorylation of RB scheduled for this cell cycle stage and arrests cells in late G1. Expression of SV40 T antigen, a transforming protein that binds underphosphorylated RB, does not block the effect of TGF-β1 on RB phosphorylation but greatly reduces the growth-inhibitory response to TGF-β1. TGF-β1 and RB appear to function in a common growth-inhibitory pathway in which TGF-β1 acts to retain RB in the underphosphorylated, growth-suppressive state.",

author = "Marikki Laiho and DeCaprio, {James A.} and Ludlow, {John W.} and Livingston, {David M.} and Joan Massague",

note = "Funding Information: We thank Dr. Frank Traganos for flow cytometry analyses. This work was supported by grants to J. M. and D. M. L. from the National Cancer Institute. M. L. was supported by the Academy of Finland.",

year = "1990",

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doi = "10.1016/0092-8674(90)90251-9",

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T1 - Growth inhibition by TGF-β linked to suppression of retinoblastoma protein phosphorylation

AU - Laiho, Marikki

AU - DeCaprio, James A.

AU - Ludlow, John W.

AU - Livingston, David M.

AU - Massague, Joan

N1 - Funding Information: We thank Dr. Frank Traganos for flow cytometry analyses. This work was supported by grants to J. M. and D. M. L. from the National Cancer Institute. M. L. was supported by the Academy of Finland.

PY - 1990/7/13

Y1 - 1990/7/13

N2 - The growth-suppressive function of the retinoblastoma gene product, RB, has been ascribed to the underphosphorylated RB form that prevails during G1 phase in the cell cycle. We show that addition of the paracrine growth inhibitor transforming growth factor β1 (TGF-β1) to Mv1Lu lung epithelial cells in mid to late G1 prevents phosphorylation of RB scheduled for this cell cycle stage and arrests cells in late G1. Expression of SV40 T antigen, a transforming protein that binds underphosphorylated RB, does not block the effect of TGF-β1 on RB phosphorylation but greatly reduces the growth-inhibitory response to TGF-β1. TGF-β1 and RB appear to function in a common growth-inhibitory pathway in which TGF-β1 acts to retain RB in the underphosphorylated, growth-suppressive state.

AB - The growth-suppressive function of the retinoblastoma gene product, RB, has been ascribed to the underphosphorylated RB form that prevails during G1 phase in the cell cycle. We show that addition of the paracrine growth inhibitor transforming growth factor β1 (TGF-β1) to Mv1Lu lung epithelial cells in mid to late G1 prevents phosphorylation of RB scheduled for this cell cycle stage and arrests cells in late G1. Expression of SV40 T antigen, a transforming protein that binds underphosphorylated RB, does not block the effect of TGF-β1 on RB phosphorylation but greatly reduces the growth-inhibitory response to TGF-β1. TGF-β1 and RB appear to function in a common growth-inhibitory pathway in which TGF-β1 acts to retain RB in the underphosphorylated, growth-suppressive state.

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Growth inhibition by TGF-β linked to suppression of retinoblastoma protein phosphorylation

Abstract

ASJC Scopus subject areas

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