Cdk2-dependent phosphorylation of NF-Y links the p53-p21 pathway to cdk1 and G2 checkpoint regulations

다국어 초록 (Multilingual Abstract)

Sequential activation and inactivation of cell cycle-dependent kinases(cdk) ensure orderly progression of the cell cycle. In this study, we demonstrate that cdk2 regulates cdk1 and the G2 checkpoint through phosphorylation of the transcription factor, NF-Y. Cdk2, but not cdk1 or cdk4, phosphorylates two serine residues near the DNA-binding domain in the YA subunit of NF-Y during S and G2 phases of the cell cycle. This phosphorylation appears to be essential for the DNA binding activity of NF-Y and the expression of NF-Y targets, including the S- and G2specific genes, and consequently for cell cycle progression at both G1 and G2/M. DNA damage leads to a decrease in YA phosphorylation and NF-Y target gene expression in the presence of p21 gene. Our results facilitate the elucidation of the molecular mechanism employed by the p21-cdk2 pathway to regulate cdk1 activity throughout the cell cycle, and at G1 and G2 checkpoint arrests following DNA damage.