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 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.
Experimental Oncology Department, Istituto Regina Elena, IRCCS, Rome, Italy.
Aymone
A
Gurtner
Paola
P
Fuschi
Fabio
F
Martelli
Isabella
I
Manni
Simona
S
Artuso
Giacoma
G
Simonte
Valeria
V
Ambrosino
Annalisa
A
Antonini
Valentina
V
Folgiero
Rita
R
Falcioni
Ada
A
Sacchi
Giulia
G
Piaggio
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D023081:CCAAT-Binding Factor; D050687:E2F1 Transcription Factor; D016159:Tumor Suppressor Protein p53