The transcription factor NF-Y is a trimer with histone-like subunits that binds and activates CCAAT-containing promoters. NF-Y controls the expression of several key regulators of the cell cycle. Repression of G2/M promoters after DNA-damage is an active mechanism that requires the p53 tumor suppressor and histone deacetylases (HDACs). We have recently found that the C-terminal Lysines of p53 are required for HDAC4 recruitment and transcriptional repression of NF-Y-dependent repressed promoters. In this study, we examined the functional and molecular effects of NF-YB knock-down. Cell cycle progression is affected with a G2/M specific depletion. This is due to the inability of activation of G2/M specific genes, as evidenced by expression profiling, RT-PCR and ChIP data. Surprisingly, apoptosis is also observed, with Caspase 3/7/8 activation. A role of p53 and Bcl-2 family members is important. NF-YB inactivation is sufficient to functionally activate p53, in the absence of DNA-damage. Failure to maintain a physiologic level of CCAAT-dependent transcription of anti-apoptotic genes contributes to impairment of Bax/Bcl-2 and Bax/Bcl-XL ratios. Our data highlight the importance of fine balancing the NF-Y-p53 duo for cell-survival by (i) maintaining transcription of anti-apoptotic genes and (ii) preventing p53 activation that triggers the apoptotic cascade.

A balance between NF-Y and p53 governs the pro- and anti-apoptotic transcriptional response / Benatti, Paolo; Basile, Valentina; Merico, Daniele; Fantoni, Luca Isaia; Tagliafico, Enrico; Mantovani, Roberto; Imbriano, Carol. - In: NUCLEIC ACIDS RESEARCH. - ISSN 1362-4962. - STAMPA. - 36:5(2007), pp. 1415-1428. [10.1093/nar/gkm1046]

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