LIN37 dependent and independent TP53 response
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB31044 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3138070.fastq.gz | Fastqsanger.gz | |||
| ERR3138080.fastq.gz | Fastqsanger.gz | |||
| ERR3138071.fastq.gz | Fastqsanger.gz | |||
| ERR3138081.fastq.gz | Fastqsanger.gz | |||
| ERR3138072.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:In order to investigate the potential role of TP53 in regulating translation, HCT116 wild type and TP53 knockout cells were analyzed using both RNA sequencing, Ribosome sequencing and nascent proteome analysis. The cells were treated with 0.2 µg/ml Neocarcinostatin (NCS) to induce DNA damage and activate TP53.
2022-04-27 | PXD029512 | Pride
Project description:The DREAM complex represses cell-cycle gene transcription in quiescence. To investigate the role of the DREAM component Lin37, we created Lin37 knockout cells by CRISPR/Cas9-nickase. pRTS episomal vectors expressing luciferase or Lin37 were introduced in two independent knockout clones (411-27 and 632-2) to create Lin37 knockout and rescue cells. To exit the cell cycle and to enter quiescence, cells were serum starved for 60h. RNA-seq was applied to identify genes de-regulated by loss of Lin37 during quiescence.
2017-08-17 | GSE97716 | GEO
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare TP53-WT and TP53-KO HCT116 cells transcriptome profiling (RNA-seq) under 5-FU treatment condition and to evaluate the correlation between transcriptome profileing and chromatin accessibility under 5-FU treatment. Methods: HCT116 cell profiles of TP53-WT and TP53- KO were generated by deep sequencing, in duplicates, using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript isoform levels: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA). Conclusions: Our study represents the detailed analysis of TP53-WT and TP53-KO HCT116 cell transcriptomes under 5-FU treatment with different timepoint, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that RNA-seq offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a TP53-WT and TP53-KO cells with and without 5-FU treatment in different timepoint. We conclude that NGS based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.
2021-02-10 | GSE157951 | GEO
Project description:The adaptor protein LNK (SH2B3) has emerged as an important protein in regulating B cell development B cell leukemia. Loss-of-function mutations in LNK (SH2B3) are found in Philadelphia chromosomeâlike acute lymphoblastic leukemia (Ph-like ALL), but how LNK regulates normal B cell development or promotes leukemogenesis remains unclear. We found that combined loss of Lnk and tumor suppressors Tp53 in mice triggers a highly aggressive and transplantable precursor B-ALL. This study aims to investigate the molecular mechanism by which LNK regulates B-ALL development. We performed expression profiling of bone marrow proB progenitors from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. Results suggest that Tp53-/-Lnk-/- B-ALLs display similar gene expression profiles to human Ph-like B-ALLs, suggesting this model for preclinical and molecular studies. B220+CD19+CD43+AA4.1+IgM-NK1.1-Ly6c- bone marrow proB cells were double sorted from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. RNA was isolated using miRNeasy kit from QIAGEN and processed using the NuGEN Pico kit. The microarray analysis was performed at the PENN Molecular Profiling/Genomics Facility using GeneChip Mouse Gene 2.0ST array (Affymetrix).
2016-04-01 | E-GEOD-76940 | biostudies-arrayexpress
Project description:SARS-CoV-2 induces widespread transcriptomic changes in host cells upon infection, in part through activation and modulation of innate immunity pathways and downstream gene regulation. However, the mechanisms by which SARS-CoV-2 and its evolutionary variants differentially affect host cell transcriptomic states remain largely unclear. Through chromatin proteomic (iDAPT-MS) analysis, we found that although SARS-CoV-2 and other pathogenic coronaviruses exhibit similar proteomic shifts on chromatin, SARS-CoV-2 uniquely promotes TP53 nuclear accumulation and activation. Parallel assessment of SARS-CoV-2 viral protein expression on host chromatin states (ATAC-seq) identifies intracellular spike protein as a key determinant of virus-mediated chromatin accessibility changes. Multilevel chromatin profiling reveals increased TP53 nuclear accumulation, TP53-associated chromatin accessibility changes, and TP53 target gene activation upon expression of SARS-CoV-2 alpha (B.1.1.7) and delta (B.1.617.2) spike variants relative to the ancestral spike sequence. TP53, ACE2, and furin cleavage are required for these changes, driving decreased cellular proliferation, increased cellular senescence, and increased cytokine release. Finally, BA.1 but not BA.2, BA.2.12.1, nor BA.4/BA.5 spike expression leads to attenuated TP53 activity and fusogenicity relative to ancestral spike. Our findings implicate spike-mediated host TP53 activation as a “rheostat” of COVID-19 pathogenicity.
2023-09-09 | PXD034648 | Pride
Project description:The adaptor protein LNK (SH2B3) has emerged as an important protein in regulating B cell development B cell leukemia. Loss-of-function mutations in LNK (SH2B3) are found in Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL), but how LNK regulates normal B cell development or promotes leukemogenesis remains unclear. We found that combined loss of Lnk and tumor suppressors Tp53 in mice triggers a highly aggressive and transplantable precursor B-ALL. This study aims to investigate the molecular mechanism by which LNK regulates B-ALL development. We performed expression profiling of bone marrow proB progenitors from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. Results suggest that Tp53-/-Lnk-/- B-ALLs display similar gene expression profiles to human Ph-like B-ALLs, suggesting this model for preclinical and molecular studies.
2016-04-01 | GSE76940 | GEO
Project description:In the present study we show that in the subset of acute myeloid leukemias (AML) with mutations in TP53, associated with poor prognosis, DNMTis, important drugs for treatment of AML, enable expression of ERVs and IFN and inflammasome signaling in a STING1 dependent manner. We previously reported in solid tumors that PARPis combined with DNMTis induce an IFN/inflammasome response that is dependent on STING1 and is mechanistically linked to generation of a homologous recombination defect (HRD). We now show that STING1 activity is actually increased in TP53 mutant compared with WT TP53 AML. Moreover, in TP53 mutant AML, STING1-dependent IFN/inflammatory signaling is increased by DNMTi treatment, whereas in AMLs with wild-type (WT) TP53, DNMTis alone have no effect. However, while combining DNMTis with PARPIs now increases IFN/inflammatory gene expression in WT TP53 AML cells, signaling induced in TP53 mutant AML is still several-fold higher. Notably, induction of HRD in both TP53 mutant and WT AMLs follows the pattern of STING1-dependent IFN and inflammatory signaling we have observed with drug treatments. These findings increase our understanding of the mechanisms that underlie DNMTi+PARPi treatment, and also DNMTi combinations with immune therapies, and a personalized approach, stratifying by p53 status, for use of such therapies, including potential immune activation of STING1 in AML and other cancers.
2022-03-07 | GSE197405 | GEO
Project description:Next Generation Sequencing Facilitates Quantitative Analysis of TP53-WT and TP53-KO HCT116 cells transcriptomes [RNA-seq]
| PRJNA663474 | ENA
Project description:A wealth of proteogenomic data has been generated using cancer samples to deepen our understanding of the mechanisms of cancer and how biological networks are altered in association with somatic mutation of tumor suppressor genes, such as TP53 and PTEN. To generate functional signatures of TP53 or PTEN loss, we profiled the RNA and phosphoproteomes of the MCF10A epithelial cell line, along with its congenic TP53- or PTEN-knockout derivatives, upon perturbation with the monofunctional DNA alkylating agent methyl methanesulfonate (MMS) vs. mock-treatment. To enable quantitative and reproducible mass spectrometry data generation, the cell lines were SILAC-labeled (stable isotope labeling with amino acids in cell culture), and the experimental design included label swapping and biological replicates. All data are publicly available and may be used to advance our understanding of the TP53 and PTEN tumor suppressor genes and to provide functional signatures for bioinformatic analyses of proteogenomic datasets.
2023-11-20 | PXD028494 | Pride
Project description:Determining the balance between DNA double strand break repair (DSBR) pathways is essential for understanding treatment response in cancer. We report a novel method for simultaneously measuring non-homologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ). This approach revealed enhanced MMEJ and HR in glioblastoma (GBM) xenograft models with acquired temozolomide (TMZ) resistance. Knockdown of proteins in either pathway enhanced killing by TMZ, and a targeted screen identified pharmacological-grade dual HR/MMEJ inhibitors, including AZD1390, an ATM kinase inhibitor. AZD1390 suppressed DSB end resection, blocked phosphorylation of end protection proteins in response to DNA damage, and potentiated TMZ in treatment-naïve and treatment-resistant models. TP53-mutant GBMs were most susceptible to AZD1390 in combination with DNA-damaging agents due to elevated ATM-dependent HR/MMEJ, preferential activation of these pathways in response to DNA damage, and a defective G2/M checkpoint, which caused these GBMs to enter mitosis despite unrepaired DNA damage, leading to cell death via apoptosis. This report establishes ATM-dependent HR and MMEJ as targetable resistance mechanisms in TP53-mutant GBM and establishes an approach for simultaneously measuring multiple DSBR pathways in treatment selection and oncology research.
2024-03-08 | PXD047837 | Pride