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| Status |
Public on Aug 01, 2020 |
| Title |
Suppression of p53 response by blocking p53–Mediator binding with a stapled peptide |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
DNA-binding transcription factors (TFs) have been challenging to target with molecular probes. Many TFs function in part through interaction with Mediator; we sought to block p53 function by disrupting the p53-Mediator interaction. Through rational design and activity-based screening, we characterized a stapled peptide, with functional mimics of both p53 activation domains, that selectively disrupted p53- and Mediator-dependent transcription in vitro. This “bivalent peptide” also suppressed p53 transcriptional response in human cancer cells. Our strategy circumvents the TF and instead targets the TF-Mediator interface, with desired transcriptional outcomes. Different TFs target Mediator through different subunits, suggesting this strategy could be generalizable.
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| |
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| Overall design |
Examination of p53 transcriptional activity by RNAseq with and without the inhibitory peptide in the presense of the p53 activator Nutlin3a.
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| Contributor(s) |
Levandowski C, Allen B, Rubin J, Read T |
| Citation(s) |
35385747 |
| |
| Submission date |
Aug 15, 2019 |
| Last update date |
May 05, 2022 |
| Contact name |
Dylan J Taatjes |
| E-mail(s) |
[email protected]
|
| Organization name |
University of Colorado at Boulder
|
| Department |
Biochemistry
|
| Lab |
Taatjes
|
| Street address |
3415 Colorado Ave JSC Biotechnology Building Campus Box 596
|
| City |
Boulder |
| State/province |
CO |
| ZIP/Postal code |
80303-0596 |
| Country |
USA |
| |
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| Platforms (1) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA560381 |
| SRA |
SRP218439 |
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