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| Status |
Public on Mar 01, 2023 |
| Title |
p53 dimers elicit unique tumor suppressive activities through an altered metabolic program [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Cancer-related alterations of the p53 Tetramerization Domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers. These are also normal p53 states under basal cellular conditions. However, their physiological relevance is not well understood. We have established in vivo models for monomeric and dimeric p53 which model Li-Fraumeni Syndrome patients with germline p53 TD alterations. p53 monomers are inactive forms of the protein. Unexpectedly, p53 dimers conferred some tumor suppression that is not mediated by canonical WT p53 activities. p53 dimers upregulate the PPAR pathway. These activities are associated with lower prevalence of thymic lymphomas and inhibition of CD8+ T-cell accumulation. Lymphomas derived from dimeric p53 mice show cooperating alterations in the PPAR pathway, further implicating a role for these activities in tumor suppression. Our data reveal novel functions for p53 dimers and support the exploration of PPAR agonists as therapies.
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| |
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| Overall design |
ChIP-sequencing for dimeric p53 (p53AD) and PPAR-alpha in p53AD basal thymus tissues
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| |
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| Contributor(s) |
Gencel-Augusto J, Lozano G |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Dec 14, 2022 |
| Last update date |
Mar 04, 2023 |
| Contact name |
Yuan Qi |
| E-mail(s) |
yqi1@mdanderson.org
|
| Organization name |
University of Texas M.D. Anderson Cancer Center
|
| Department |
Bioinformatics & Computational Biology
|
| Street address |
1400 Pressler St
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030-4008 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE220966 |
p53 dimers elicit unique tumor suppressive activities through an altered metabolic program |
|
| Relations |
| BioProject |
PRJNA912179 |
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