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. In this study, we examined the functional and molecular effects of NF-YB knockdown. 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 cleavage. 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.
Titolo: | A balance between NF-Y and p53 governs the pro- and anti-apoptotic transcriptional response |
Autori: | |
Parole Chiave: | NF-Y ; p53 ; CCAAT box ; apoptosis ; cell cycle |
Settore Scientifico Disciplinare: | Settore BIO/10 - Biochimica |
Data di pubblicazione: | 2008 |
Rivista: | |
Tipologia: | Article (author) |
Digital Object Identifier (DOI): | 10.1093/nar/gkm1046 |
Appare nelle tipologie: | 01 - Articolo su periodico |