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| Status |
Public on Jun 01, 2015 |
| Title |
Che-1 modulates the decision between cell cycle arrest and apoptosis by its binding to p53. |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The tumor suppressor p53 is mainly involved in the transcriptional regulation of a large number of growth-arrest- and apoptosis-related genes. However, a clear understanding of which factor/s influences the choice between these two opposing p53- dependent outcomes remains largely elusive. We have previously described that in response to DNA damage, the RNA polymerase II binding protein Che-1/AATF transcriptionally activates p53. Here, we show that Che-1 binds directly p53. This interaction essentially occurs in the first hours of DNA damage, whereas it is lost when cells undergo to apoptosis in response to post-transcriptional modifications. Moreover, Che-1 sits in a ternary complex with p53 and the oncosuppressor Brca1. Accordingly, our analysis of genome-wide chromatin occupancy by p53 revealed that p53/Che1 interaction results in preferential transactivation of growth-arrest p53 target genes over its pro-apoptotic target genes. Notably, exposure of Che-1+/- mice to ionizing radiations resulted in enhanced apoptosis of thymocytes, compared to wild-type mice. These results confirm Che-1 as an important regulator of p53 activity and suggest Che-1 to be a promising yet attractive drug target for cancer therapy.
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| Overall design |
ChIP-Seq for p53 in control (DNA damage, IR) and Che-1 depleted Hct116 cells
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| Contributor(s) |
Desantis A, Bruno T, Catena V, De Nicola F, Goeman F, Pallocca M, D' Onorio De Meo P, Fanciulli M |
| Citation(s) |
25996291 |
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| Submission date |
Aug 08, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Matteo Pallocca |
| Organization name |
Italian National Cancer Institute "Regina Elena"
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| Street address |
Via Fermo Ognibene
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| City |
Rome |
| ZIP/Postal code |
00144 |
| Country |
Italy |
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| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA257888 |
| SRA |
SRP045381 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE60267_RAW.tar |
393.8 Mb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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