Negative regulation of G1 in mammalian cells: inhibition of cyclin E-dependent kinase by TGF-beta

Science. 1993 Apr 23;260(5107):536-9. doi: 10.1126/science.8475385.


Transforming growth factor-beta (TGF-beta) is a naturally occurring growth inhibitory polypeptide that arrests the cell cycle in middle to late G1 phase. Cells treated with TGF-beta contained normal amounts of cyclin E and cyclin-dependent protein kinase 2 (Cdk2) but failed to stably assemble cyclin E-Cdk2 complexes or accumulate cyclin E-associated kinase activity. Moreover, G1 phase extracts from TGF-beta-treated cells did not support activation of endogenous cyclin-dependent protein kinases by exogenous cyclins. These effects of TGF-beta, which correlated with the inhibition of retinoblastoma protein phosphorylation, suggest that mammalian G1 cyclin-dependent kinases, like their counterparts in yeast, are targets for negative regulators of the cell cycle.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CDC2-CDC28 Kinases*
  • Cell Extracts
  • Cell Line
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases*
  • Cyclins / metabolism*
  • Cyclins / pharmacology
  • Enzyme Activation / drug effects
  • G1 Phase*
  • Mink
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases*
  • Retinoblastoma Protein / metabolism
  • Transforming Growth Factor beta / pharmacology*


  • Cell Extracts
  • Cyclins
  • Retinoblastoma Protein
  • Transforming Growth Factor beta
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases