A balance between NF-Y and p53 governs the pro- and anti-apoptotic transcriptional response
Open Access
- 10 January 2008
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 36 (5), 1415-1428
- https://doi.org/10.1093/nar/gkm1046
Abstract
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-X L 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.Keywords
This publication has 61 references indexed in Scilit:
- Inhibition of CBF/NF-Y mediated transcription activation arrests cells at G2/M phase and suppresses expression of genes activated at G2/M phase of the cell cycleNucleic Acids Research, 2006
- Dynamic recruitment of transcription factors and epigenetic changes on the ER stress response gene promotersNucleic Acids Research, 2006
- Repression of New p53 Targets Revealed by ChIP on Chip ExperimentsCell Cycle, 2006
- DNA Damage Promotes Histone Deacetylase 4 Nuclear Localization and Repression of G2/M Promoters, via p53 C-terminal LysinesPublished by Elsevier BV ,2006
- The promoters of human cell cycle genes integrate signals from two tumor suppressive pathways during cellular transformationMolecular Systems Biology, 2005
- Cell-Cycle Regulation of NF-YC Nuclear LocalizationCell Cycle, 2004
- Cdk2-dependent Phosphorylation of the NF-Y Transcription Factor and Its Involvement in the p53-p21 Signaling PathwayPublished by Elsevier BV ,2003
- Significance analysis of microarrays applied to the ionizing radiation responseProceedings of the National Academy of Sciences of the United States of America, 2001
- Cell-cycle regulation of the DNA topoisomerase IIα promoter is mediated by proximal CCAAT boxes: possible involvement of acetylationGene, 2000
- Weight matrix descriptions of four eukaryotic RNA polymerase II promoter elements derived from 502 unrelated promoter sequencesJournal of Molecular Biology, 1990