Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Using ribosome profiling to investigate the effect of p53 on translation in cancer cells

ABSTRACT: p53 is deleted or dysfunctional, or develops these features during the course of disease, with a frequency of about 50% in human cancers. This is clinically important because this group of patients respond very poorly to treatment. Our approach to discovering novel biomarkers or targets for therapy for p53 deleted/dysfunctional disease is to find genes that are translationally regulated by p53. The aim of this experiment is to compare translational efficiencies in cancer cells that are p53 WT, p53-/-, or p53 R175H, in response to doxorubicin.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Homo sapiens

SUBMITTER: Anne Willis

PROVIDER: E-MTAB-8100 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

BRD7 is a candidate tumour suppressor gene required for p53 function

Project description:Oncogene-induced senescence (OIS) is a p53-dependent defence mechanism against uncontrolled proliferation. Consequently, many human tumours harbour p53 mutations while others show a dysfunctional p53 pathway, frequently by unknown mechanisms. We identified BRD7, a bromodomain-containing protein whose inhibition allows full neoplastic transformation in the presence of wild-type p53. Intriguingly, in human breast tumours harbouring wild-type, but not mutant p53, the BRD7 gene locus was frequently deleted and low BRD7 expression was found in a subgroup of tumours. Functionally, BRD7 is required for efficient p53-mediated transcription of a subset of target genes. BRD7 interacts with p53 and p300, and is recruited to target gene promoters, affecting histone acetylation, p53 acetylation, and promoter activity. Thus, BRD7 suppresses tumourigenicity by serving as a p53 cofactor required for efficient induction of p53-dependent OIS. We recorded mRNA expression profiles of BJ primary fibroblasts expressing the oncogene RasV12 and either control vector, one of two BRD7 knockdown vectors, or p53 knockdown vector. In addition, we profiled genome-wide protein DNA interactions for p53 and BRD7 using ChIP-Seq. p53- and BRD7-binding sites were recorded in RasV12-expressing BJ cells; as a control we used knockdown of the gene of interest (BRD7 or p53).

2010-03-14 | E-GEOD-20076 | biostudies-arrayexpress

RNA-seq of cell lines containing p53-R273H or p53-R273H 22/23

Project description:RNA-sequencing was performed to determine the differences between cells that contain mutant p53 and a transactivation deficient mutant of p53 to determine why the TAD mutant cells don't form tumors.

2020-12-18 | E-MTAB-9833 | 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

Structural Assessment of the Full-Length Tumor Suppressor Protein p53 by Mass Spectrometry-Guided Computational Modeling

Project description:The tetrameric tumor suppressor p53 represents a great challenge for 3D structural analysis due to its high degree of intrinsic disorder (ca. 40%). We developed and applied an integrative structural biology approach combining complementary techniques of structural mass spectrometry (MS), namely cross-linking mass spectrometry (XL-MS), protein footprinting, and hydrogen/deuterium exchange mass spectrometry (HDX-MS), with advanced protein structure prediction approaches to gain insights into the disordered C-terminal region of p53. Additionally, we evaluate possible differences in p53 regarding solvent accessibility and topology upon DNA binding. Our quantitative XL-MS and lysine labeling data show no major conformational differences in p53 between DNA-bound and DNA-free states. Integration of experimental data generate p53 models for p53’s intrinsically disordered regions (IDRs) that reflect substantial compaction of the molecule. Our models provide the most detailed description of the relationship between p53’s folded regions and IDRs that is available to date. The synergies between complementary structural MS techniques and computational modeling as pursued in our integrative approach is envisioned to serve as general strategy for studying intrinsically disordered proteins (IDPs) and IDRs.

2023-06-26 | PXD037030 | 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

p53 C-terminal acetylation modulates apoptotic program

Project description:Advanced colorectal cancer (CRC) is an unresolved clinical problem. Epigenetic drugs belonging to the group of histone deacetylase inhibitors (HDACi) may combat CRC in rationally designed treatment schedules. Unfortunately, there is sparse evidence on molecular mechanisms and markers that determine cellular sensitivity to HDACi. Irinotecan is widely used to treat CRC and causes replication stress (RS) and DNA damage as topoisomerase-I inhibitor. We applied irinotecan and the class I HDACi entinostat (MS-275) to isogenic p53-positive and -negative CRC cells. Combinations of irinotecan and MS-275 evoke mitochondrial damage, caspase-mediated apoptosis, and RS-associated DNA damage synergistically and p53-dependently. Targeted mass spectrometry and immunoblot show that irinotecan induces phosphorylation, acetylation, and accumulation of p53 and its target genes. Addition of MS-275 augments the irinotecan-induced acetylation of C-terminal lysine residues of p53 but decreases its phosphorylation and p53 target gene induction. Furthermore, MS-275 increases the amount of acetylated p53 at mitochondria and dysregulates the expression of pro- and anti-apoptotic BCL2 proteins in irinotecan-treated cells. Regarding DNA repair, we see that MS-275 represses the homologous recombination (HR) filament protein RAD51, which limits DNA damage and pro-apoptotic effects of irinotecan. These data suggest that key class I HDAC-dependent functions of p53 in cells with RS are linked to mitochondrial damage and a breakdown of HR. Most importantly, combinations of irinotecan plus MS-275 also kill short-term primary CRC cell cultures and organoids from CRC patients but spare organoids of adjacent matched normal tissue. Thus, irinotecan/HDACi treatment is a promising new approach for the therapy of p53-proficient tumors with clinically tractable inhibitors.

2022-02-15 | PXD019999 | Pride

PINT lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb Repressive Complex 2 (MEF cells)

Project description:It has been recently shown that the transcription factor p53 induces the expression of multiple lincRNAs. However, relatively little is known about the role that lincRNAs play in this pathway. Here we characterize a lincRNA named PINT (p53 Induced Noncoding Transcript). We show that PINT is a ubiquitously expressed lincRNA that is finely regulated by p53. In mouse cells, PINT promotes cell proliferation and survival by regulating the expression of genes of TGF-beta, MAPK and p53 pathways. PINT is a nuclear lincRNA that directly interacts with Polycomb Repressive Complex 2 (PRC2), being required for PRC2 targeting of specific genes for repression. Furthermore, PINT functional activity is dependent on PRC2 expression, representing a connection between the p53 pathway and epigenetic regulation by PRC2. We have also identified PINT human ortholog (hPINT), which presents suggestive analogies with the mouse lincRNA. hPINT is similarly regulated by p53, and its expression correlates significantly with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, hPINT is significantly downregulated in colon cancer, representing a novel tumor suppressor candidate. Our results not only help our understanding of the role of p53 and lincRNAs in cancer, but also contribute to the open debate regarding the utility of mouse models for the study of lincRNAs. Inhibition of PINT or p53 gene expression and subsequent treatment with 150 nM doxorubicine for 12h in MEF LSL p53 +/+ cells.

2013-08-09 | E-GEOD-46247 | 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

Bulk RNA-Seq to study the effects of CENP-A overexpression, p53 status, and X- irradiation treatment in MCF-10-2A cells

Project description:We performed bulk RNA-Seq to investigate global transcriptional changes upon overexpression of the centromeric H3 variant CenH3/CENP-A in p53 wild-type and defective cells, and after X-irradiation treatment. We established clonal MCF-10-2A TetOn-CENPA-FLAG-HA cell lines where CENP-A can be reversibly induced by Doxycycline (Dox) treatment. Upon CENP-A overexpression, these cells exhibit different radiosensitivity depending on p53 status. In order to profile global changes in expression, we compared MCF-10-2A TetOn-CENPA-FLAG-HA cells expressing either empty vector (p53-WT) or dominant-negative p53 (p53-DN) with 0X Dox (no Dox), 1X Dox (10 ng/ml), or 10X Dox (100 ng/ml) for 24h. At time 0, we irradiated one set of cells by X-ray generator (4gy) while a control set remained un-irradiated (0gy). 6h later, we extracted RNA for RNA-seq.

2021-03-01 | E-MTAB-9867 | biostudies-arrayexpress

Cross-Species Comparison Identifies Proneural specific patterns of genetic alterations in Glioblastoma

Project description:The determinants of the genetic complexity of Glioblastoma are poorly understood. We generated murine Glioblastomas by transforming glial progenitors in the adult brain with PDGF expression and PTEN deletion +/- p53 deletion. PDGF+PTEN-/- tumors developed additional deletions of specific genes in up to 100% of the tumors, whereas PDGF+PTEN-/-p53-/- tumors did not. Cross-species comparison with data from tCGA database and published in Verhaak, 2010, showed that consistent genetic deletions observed in mouse tumors were specific to human Proneural Glioblastoma. These findings show that the genetic alterations that accumulate during tumor progression are determined by the initiating genetic alterations and by the cellular context in which they occur. Murine gliomas were induced in vivo by retroviral mediated PDGF overexpression, PTEN deletion with or without p53 deletion using Cre/lox system. Tumors were subsequently harvested for sequencing and aCGH analysis. Paired liver DNA was used for hybridization. For PDGF+PTEN-/- tumors, different timepoints were obtained including 21, 35 days post tumor induction, as well as endstage tumors.

2014-01-17 | E-GEOD-36940 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data