Cdk2-dependent phosphorylation of the NF-Y transcription factor and its involvement in the p53-p21 signaling pathway

J Biol Chem. 2003 Sep 19;278(38):36966-72. doi: 10.1074/jbc.M305178200. Epub 2003 Jul 11.


Recent studies have suggested that the NF-Y transcription factor is involved in transcription repression of the cell cycle regulatory genes in a response to p53 induction or DNA damage. Here we demonstrate the cdk2-dependent phosphorylation of NF-Y and its involvement in transcription repression by the p53-p21 signaling pathway. Cdk2 phosphorylates two serine residues near the DNA-binding domain of the YA subunit of NF-Y. Cyclin A-cdk2 appears to associate with NF-Y both in vitro and in vivo. Furthermore, YA protein is phosphorylated in parallel with a cell cycle-dependent activation of cdk2 kinase and cyclin A expression. YA phosphorylation is unnecessary for heterotrimer formation with the YB-YC dimer. However, NF-Y containing a phosphorylation-deficient mutant form of YA, YA-aa, has its DNA binding activity impaired. Consistently, YA-aa inhibits transcription activation of a NF-Y target promoter, cdc2, by cdk2. These results facilitate the elucidation of the regulatory mechanisms of cell cycle progression involving the p21-cdk2-NF-Y signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • CCAAT-Binding Factor / metabolism*
  • CDC2-CDC28 Kinases / metabolism*
  • Cell Cycle
  • Cell Line
  • Cell Nucleus / metabolism
  • Cyclin A / metabolism
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism*
  • DNA Damage
  • Dimerization
  • Glutathione Transferase / metabolism
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation*
  • Plasmids / metabolism
  • Precipitin Tests
  • Promoter Regions, Genetic
  • Protein Binding
  • Purines / pharmacology
  • Roscovitine
  • Serine / chemistry
  • Signal Transduction*
  • Time Factors
  • Transfection
  • Tumor Suppressor Protein p53 / metabolism*


  • CCAAT-Binding Factor
  • CDKN1A protein, human
  • Cyclin A
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Purines
  • Tumor Suppressor Protein p53
  • Roscovitine
  • Serine
  • Glutathione Transferase
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2