TGFβ inhibition of Cdk4 synthesis is linked to cell cycle arrest

doi:10.1016/0092-8674(93)90723-4

Cell

Volume 74, Issue 6, 24 September 1993, Pages 1009-1020

https://doi.org/10.1016/0092-8674(93)90723-4 Get rights and content

Abstract

Transforming growth factor β1 (TGFβ1) causes G1 growth arrest and the accumulation of unphosphorylated retinoblastoma protein (Rb) in responsive cells. Cdk4 (cyclin-dependent kinase), a major catalytic subunit of the mammalian D-type G1 cyclins, can phosphorylate Rb in vitro, and at least one D-type cyclin, D2, directs the phosphorylation of Rb in vivo. Here we show that TGFβ1 induces suppression of cdk4 synthesis in G1 in mink lung epithelial cells. Constitutive cdk4 synthesis in these cells led to TGFβ1 resistance. It also resulted in growth in low serum medium when these cells were released from contact inhibition. Cdk2 activity was also suppressed by TGFβ1 action, but its constitutive expression failed to override a TGFβ1-induced G1 block. Hence, the TGFβ1 block is primarily mediated by cdk4 modulation. Further evidence suggests that TGFβ1-induced down-modulation of cdk4 leads to inhibition of cdk2 activation and that both events might contribute to TGFβ1 growth suppression.

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ArticleTGFβ inhibition of Cdk4 synthesis is linked to cell cycle arrest

Abstract

Biochim. Biophys. Acta

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J. Virol.

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Genomics

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T. Cell

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Growth factors and cancer

Science

Transforming growth factor β1 (TGFβ1) reduces cellular levels of p34cdc2, and this effect is abrogated by adenovirus independently of the E1A-associated pRB binding activity

Mol. Biol. Cell

Independent regulation of human D-type cyclin gene expression during G1 phase in primary human T lymphocytes

J. Cell Biol.

Suppression of growth factor-induced CYL1 cyclin gene expression by antiproliferative agents

J. Biol. Chem.

Article
TGFβ inhibition of Cdk4 synthesis is linked to cell cycle arrest