Nuclear factor Y (NF-Y) and cellular senescence

NF-Y, also termed CBF, is a major CCAAT-binding transcription factor that specifically recognizes the consensus sequence 5'-CTGATTGGYYRR-3 or 5'-YYRRCCAATCAG-3' (Y = pyrimidines and R = purines) present in the promoter region of many constitutive, inducible, and cell-cycle-dependent eukaryotic genes. The functional NF-Y is a heterotrimeric protein, consisting of three different subunits, A, B, and C. Each of the three subunits contains two or three distinct protein-interacting domains for trimer formation and for interacting with other nuclear proteins. Only the trimeric NF-Y, and not the individual subunit, possess DNA-binding activity. The transcriptional activity of NF-Y can be regulated by differential expression, alternative splicing, protein-protein interactions, and cellular redox potential. The regulation of thymidine kinase (TK) and dihydrofolate reductase (DHFR) genes in human diploid fibroblasts serves as an example of how NF-Y may have a role in replicative senescence by regulating age-dependent G1/S genes.