Transcription Factor NF-Y Induces Apoptosis in Cells Expressing Wild-Type p53 through E2F1 Upregulation and p53 Activation

The CCAAT-binding transcription factor NF-Y plays a central role in regulating cellular proliferation by controlling the expression of genes required for cell-cycle progression such as cyclin A, cyclin B1, cyclin B2, cdc25A, cdc25C, and cdk1. Here we show that unrestricted NF-Y activity leads to apo...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2010-12, Vol.70 (23), p.9711-9720
Main Authors: GURTNER, Aymone, FUSCHI, Paola, SACCHI, Ada, PIAGGIO, Giulia, MARTELLI, Fabio, MANNI, Isabella, ARTUSO, Simona, SIMONTE, Giacoma, AMBROSINO, Valeria, ANTONINI, Annalisa, FOLGIERO, Valentina, FALCIONI, Rita
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Apoptosis - physiology
Biological and medical sciences
Blotting, Western
CCAAT-Binding Factor - genetics
CCAAT-Binding Factor - metabolism
CCAAT-Binding Factor - physiology
Cell Line
Cell Line, Tumor
Cell Proliferation
Cells, Cultured
E2F1 Transcription Factor - genetics
E2F1 Transcription Factor - metabolism
Embryo, Mammalian - cytology
Fibroblasts - cytology
Fibroblasts - metabolism
HCT116 Cells
HeLa Cells
Humans
Medical sciences
Mice
Mice, Knockout
Pharmacology. Drug treatments
Reverse Transcriptase Polymerase Chain Reaction
RNA Interference
Signal Transduction - physiology
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The CCAAT-binding transcription factor NF-Y plays a central role in regulating cellular proliferation by controlling the expression of genes required for cell-cycle progression such as cyclin A, cyclin B1, cyclin B2, cdc25A, cdc25C, and cdk1. Here we show that unrestricted NF-Y activity leads to apoptosis in an E2F1- and wild-type p53 (wtp53)-dependent manner. Unrestricted NF-Y activity induced an increase in E2F1 mRNA and protein levels. Furthermore, NF-Y directly bound the E2F1 promoter and this correlated with the appearance of open chromatin marks. The ability of NF-Y to induce apoptosis was impaired in cells lacking E2F1 and wtp53. Moreover, NF-Y overexpression elicited phosphorylation of wt p53Ser18 in an E2F1-dependent manner. Our findings establish that NF-Y acts upstream of E2F1 in p53-mediated apoptosis.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-10-0721