Cdk2-dependent phosphorylation of the NF-Y transcription factor and its involvement in the p53-p21 signaling pathway.
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.
Yun
Jeanho
J
National Research Laboratory, Department of Microbiology, Dankook University College of Medicine, Cheonan, 330-714, Korea.
Chae
Hee-Don
HD
Choi
Tae-Saeng
TS
Kim
Eun-Hee
EH
Bang
Yung-Jue
YJ
Chung
Jongkyeong
J
Choi
Kyeong-Sook
KS
Mantovani
Roberto
R
Shin
Deug Y
DY
D000595:Amino Acid Sequence; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D042846:CDC2-CDC28 Kinases / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D019925:Cyclin A / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004249:DNA Damage; D019281:Dimerization; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011687:Purines / Q000494:pharmacology; D000077546:Roscovitine; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D023081:CCAAT-Binding Factor; C493956:CDKN1A protein, human; D019925:Cyclin A; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011687:Purines; D016159:Tumor Suppressor Protein p53; D000077546:Roscovitine; D012694:Serine; D005982:Glutathione Transferase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2