Nucleic Acids Research Advance Access published online on January 10, 2008
Nucleic Acids Research, doi:10.1093/nar/gkm1046
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Molecular Biology |
A balance between NF-Y and p53 governs the pro- and anti-apoptotic transcriptional response
1Dipartimento di Biologia Animale, Università di Modena e Reggio, Via Campi 213/d, 41100 Modena, 2Dipartimento di Scienze Biomolecolari e Biotecnologie, Università di Milano, Via Celoria 26, 20133 Milano and 3Dipartimento di Scienze Biomediche, Università di Modena e Reggio, Via Campi 287, 41100 Modena, Italy
*To whom correspondence should be addressed. Tel: +39 059 2055542; Fax: +39 059 2055548; Email: cimbriano{at}unimo.it
Received July 24, 2007. Revised November 2, 2007. Accepted November 4, 2007.
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.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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