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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

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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

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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

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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

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2024-05-10 | PXD050892 | Pride

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

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