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C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4.

The transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) is a strong inhibitor of cell proliferation. We found that C/EBPalpha directly interacts with cdk2 and cdk4 and arrests cell proliferation by inhibiting these kinases. We mapped a short growth inhibitory region of C/EBPalpha between amino acids 175 and 187. This portion of C/EBPalpha is responsible for direct inhibition of cyclin-dependent kinases and causes growth arrest in cultured cells. C/EBPalpha inhibits cdk2 activity by blocking the association of cdk2 with cyclins. Importantly, the activities of cdk4 and cdk2 are increased in C/EBPalpha knockout livers, leading to increased proliferation. Our data demonstrate that the liver-specific transcription factor C/EBPalpha brings about growth arrest through direct inhibition of cdk2 and cdk4.

Pubmed ID: 11684017

Authors

  • Wang H
  • Iakova P
  • Wilde M
  • Welm A
  • Goode T
  • Roesler WJ
  • Timchenko NA

Journal

Molecular cell

Publication Data

October 30, 2001

Associated Grants

  • Agency: NIA NIH HHS, Id: AG 00756
  • Agency: NIGMS NIH HHS, Id: GM 55188

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha
  • CDC2-CDC28 Kinases
  • Cell Division
  • Cell Fractionation
  • Cell Line
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases
  • Enzyme Inhibitors
  • Genes, Reporter
  • Liver
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Nuclear Proteins
  • Protein Structure, Secondary
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Rats
  • Recombinant Fusion Proteins