Role of the transcriprion factor NF-Y in cell cycle regulation

The CCAAT-binding factor NF-Y plays an important role in controlling the transcription of cell cycle regulated genes. NF-Y binding sites belong to the regulatory module NF-Y-CDE-CHR, which controls cell cycle-dependent transcription of G2/M genes. NF-Y functions as an heterotrimer composed by NF-YA, NF-YB and NF-YC subunits. NF-YB knock-down impairs cell cycle progression by reducing G2/M cells and inducing p53-dependent apoptosis. Failure to maintain a physiological level of anti-apoptotic genes by NF-Y transcriptional activity, contributes to the triggering of the apoptotic cascade. Increasing the levels of NF-Y expression protects cells from entering a p53-mediated apoptosis: NF-Y reverts cytochrome c release into the cytoplasm following Adriamycin treatment, preventing p53 transcriptional activation. To investigate the role of the different NF-Y subunits in controlling cell cycle progression, we have separately knocked-down the three subunits by lentiviral shRNAs. NF-YA silencing shows a more severe impairment in cell cycle progression with respect to NF-YB knock-down. p53 is a common player of the cell cycle block observed following both NF-YA and NF-YB silencing. The identification of the signaling pathways through which p53 is activated will shed light on the molecular mechanism controlling the cross-talk between NF-Y and p53.