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Series GSE135870 Query DataSets for GSE135870
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.
 
Overall design Examination of p53 transcriptional activity by RNAseq with and without the inhibitory peptide in the presense of the p53 activator Nutlin3a.
 
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) dylan.taatjes@colorado.edu
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
 
Platforms (1)
GPL21697 NextSeq 550 (Homo sapiens)
Samples (20)
GSM4036934 DMSO_H2O_exp1_rep1
GSM4036935 DMSO_H2O_exp1_rep2
GSM4036936 DMSO_Peg6_exp1_rep1
Relations
BioProject PRJNA560381
SRA SRP218439

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE135870_isoform_corrected_exp1.txt.gz 2.3 Mb (ftp)(http) TXT
GSE135870_isoform_corrected_exp2.txt.gz 3.0 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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