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Characterization of the p53 cistrome - DNA binding cooperativity dissects p53's tumor suppressor functions

ABSTRACT: p53 wildtype or complementing DNA binding cooperativity versions (EE, RR, EE/RR) were overexpressed in SAOS cells and 18h later harvested to perform ChIP with an p53-specific antibody. The enriched DNA fragments were purified and identified by high throughput sequencing.

ORGANISM(S): Homo sapiens

SUBMITTER: Thorsten Stiewe

PROVIDER: E-MTAB-1394 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Characterization of the p53 cistrome--DNA binding cooperativity dissects p53's tumor suppressor functions.

Schlereth Katharina K Heyl Charlotte C Krampitz Anna-Maria AM Mernberger Marco M Finkernagel Florian F Scharfe Maren M Jarek Michael M Leich Ellen E Rosenwald Andreas A Stiewe Thorsten T

PLoS genetics 20130815 8

p53 protects us from cancer by transcriptionally regulating tumor suppressive programs designed to either prevent the development or clonal expansion of malignant cells. How p53 selects target genes in the genome in a context- and tissue-specific manner remains largely obscure. There is growing evidence that the ability of p53 to bind DNA in a cooperative manner prominently influences target gene selection with activation of the apoptosis program being completely dependent on DNA binding coopera ...[more]

PMID: 23966881

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Characterization of the p53 cistrome - DNA binding cooperativity dissects p53's tumor suppressor functions - Expression profiling

Project description:P53 wildtype or complementing DNA binding cooperativity versions (p53EE, p53RR, p53EE/RR) were overexpressed in SAOS cells. After 18h cells were harvested and subjected to expression profiling.

2014-02-14 | E-MTAB-1403 | biostudies-arrayexpress

ChipSeq of conditional knock-in mouse carrying the R178E (EE) mutation in exon 5 of the endogenous mouse Trp53 gene locus.

Project description:The mouse R178E (EE) mutation of the Trp53 is a p53 mutant protein with native conformation that lacks the ability to form tetramers and thus constitutes a mutant form of p53 that lacks DNA binding cooperativity. Here we want to assess DNA binding ability of the EE mutant in MEFs under untreated conditions and following p53 stabilization with the Mdm2 inhibitor nutlin-3a and compare it to p53 KO and WT mice.

2019-09-03 | E-MTAB-6793 | biostudies-arrayexpress

Transcription profiling of human Soas-2 cells infected with adenoviruses expressing p53 proteins with charge-neutralizing or charge-inverting mutations in the H1 helix to investigate the role of the dimerization interface in p53 function

Project description:To investigate the role of the dimerization interface for p53 function, we introduced modest charge-neutralizing (R181→L "EL") and more severe charge-inverting (R181→E "EE" and E180→R, R181→E "RE") mutations into the H1 helix of the full-length p53 molecule. To characterize the nuclear transcriptional function of p53 mutants in an unbiased manner we employed gene expression profiling using cDNA microarrays. Saos-2 cells were infected with adenoviruses expressing the p53 proteins EE, EL, WT and RE which span the entire spectrum of apoptotic activity. Total cellular RNA was isolated 18 hours after infection when apoptosis had not yet occurred.

2010-04-01 | E-MEXP-1209 | biostudies-arrayexpress

ChIP-seq of H1299 cells stably transfected with empty vector or the p53 mutant R273H

Project description:This experiment was performed to determine which gene promoters mutant p53 binds and transcriptionally regulates in order to understand how mutant p53 accomplishes its gain of function phenotype.

2017-04-16 | E-MTAB-5653 | biostudies-arrayexpress

Human p53 interating protein ID

Project description:Wild type and mutant p53 were transfected in H1299 cells and the associated complexes were affinity purified. The p53 interacting proteins then analyzed by ms/ms.

2019-01-29 | PXD012463 | Pride

RNA-seq of H1299 cells stably transfected with empty vector or the p53 mutant R273H.

Project description:This experiment aimed to determine the genes that were upregulated when mutant p53 (R273H) was expressed. We used H1299 lung cancer cells that are endogenously p53-null and overexpressed the p53 mutant.

2017-04-16 | E-MTAB-5652 | biostudies-arrayexpress

Residual tumor suppressor activities of tumorigenic p53 mutants enhance survival under chemotherapy

Project description:p53 mutations are believed to correlate with poor patient survival, as mutations abolish the transcriptional function of wild-type p53 in the DNA damage response and mutant p53 gain-of-function activities enhance drug resistance. Moreover, p53 also exhibits non-transcriptional apoptotic activity with yet unclear in vivo relevance for tumor suppression and cancer therapy. We have generated mice expressing a unique p53 mutant (R178E, human R181E) that is DNA binding deficient without alterations in the global structure or DNA binding surface. The aim of this study is to use this new mouse model to demonstrate that a DNA binding-deficient p53 mutant can drive tumor development while retaining non-transcriptional apoptotic activities.

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2016-05-03 | PXD001673 | Pride

Structural dynamics of the E6AP/UBE3A-E6-p53 enzyme-substrate complex

Project description:Deregulation of the ubiquitin ligase E6AP is causally linked to the development of human disease, including cervical cancer. In complex with the E6 oncoprotein of human papillomaviruses, E6AP targets the tumor suppressor p53 for degradation, thereby contributing to carcinogenesis. Moreover, E6 acts as a potent activator of E6AP by a yet unknown mechanism. However, structural information explaining how the E6AP-E6-p53 enzyme-substrate complex is assembled, and how E6 stimulates E6AP, is largely missing. We therefore developed and applied different approaches in structural mass spectrometry to show that binding of E6 induces conformational rearrangements in E6AP, which result in the positioning of E6 and p53 in the immediate vicinity of the catalytic centre of E6AP. Our data provides structural and functional insights into the dynamics of the full-length E6AP-E6-p53 enzyme-substrate complex and reveals how E6 can both stimulate the ubiquitin ligase activity of E6AP and facilitate the transfer of ubiquitin from E6AP onto p53.

2018-10-23 | PXD010002 | Pride

Transcription profiling of human colorectal carcinoma-derived cell lines, p53 -/-, +/-, +/+ at 0 and 12 hrs after growth arrest

Project description:Human colorectal carcinoma-derived cell lines, p53 -/-, +/-, +/+ at 0 and 12 hrs after growth arrest.

2007-09-28 | E-GEOD-90 | biostudies-arrayexpress