Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of the RNAs that bind with MDM2 by high-throughput RIP-seq in MDA-MB-231 and MCF-7 cells

ABSTRACT: The E3 ligase MDM2 promotes tumor growth and progression by inducing ubiquitin-mediated degradation of P53 and other tumor suppressing proteins. Here, we identified an MDM2-interacting lncRNA NRON, which promotes tumor formation by suppressing both P53-dependent and independent pathways. NRON binds to MDM2 and MDMX (MDM4) via two different stem-loops respectively and induces their heterogenous dimerization, thereby enhancing the E3 ligase activity of MDM2 towards its tumor suppressing substrates, including P53, RBI and NFATI, etc.

ORGANISM(S): Homo sapiens

PROVIDER: GSE226511 | GEO | 2023/06/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data from MCF7 wildtype and MCF7 MDMXC463A/WT cells

Project description:MDMX C463A mutation disrupts its binding with MDM2, and leads insufficient of MDM2 E3 ligase activity. With that, p53 degradation would be slower. In this case, p53 remaining its tumor suppressor function without transactivation. To figure out the whole map of transcripts change in MDMX C463A mutation cells. We used MCF7 parental cells as control group, and MCF7 MDMXC463A/WT mutation cells as experimental group for gene chip analysis.

2018-01-20 | GSE109406 | GEO

Expression data from mouse embryonic fibroblasts (MEFs) mdmxER-Cre;C463A/WT cells, with or without 4-Hydroxytamoxifen (4OHT) treatment.

Project description:MDMX C463A mutation disrupts its binding with MDM2, and leads insufficient of MDM2 E3 ligase activity. With that, p53 degradation would be slower. In this case, p53 remaining its tumor suppressor function without transactivation. To figure out the whole map of transcripts change in MDMX C463A mutation MEFs. We used mdmxER-Cre;C463A/WTMEFs with EtOH treatment as control group, and same cells with 4OHT treatment as experimental group for gene chip analysis.

2018-01-20 | GSE109407 | GEO

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [HCT116 microarray]

Project description:The Mdm2 oncoprotein ubiquitinates and antagonizes p53 but may also carry out p53-independent functions. Here we report that Mdm2 is required for the efficient generation of induced pluripotent stem cells (iPSCs) from murine embryonic fibroblasts, in the absence of p53. Similarly, Mdm2 depletion in the context of p53 deficiency also promoted the differentiation of human mesenchymal stem cells and diminished clonogenic survival of cancer cells. Most of the Mdm2-controlled genes also responded to the inactivation of the Polycomb Repressor Complex 2 (PRC2) and its catalytic component EZH2. Mdm2 physically associated with EZH2 on chromatin, enhancing the trimethylation of Histone 3 at lysine 27 and the ubiquitination of Histone 2A at lysine 119 (H2AK119) at its target genes. Removing Mdm2 simultaneously with the H2AK119 E3 ligase Ring1B/RNF2 further induced these genes and synthetically arrested cell proliferation. In conclusion, Mdm2 supports the Polycomb-mediated repression of lineage specific genes independent of p53. microarray analysis in HCT116 p53-/-cells

2015-12-31 | E-GEOD-73294 | biostudies-arrayexpress

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [ChIP-Seq]

2015-12-31 | E-GEOD-73293 | biostudies-arrayexpress

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [hMSC microarray]

2015-12-31 | E-GEOD-73601 | biostudies-arrayexpress

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [RNA-Seq]

2015-12-31 | E-GEOD-73176 | biostudies-arrayexpress

MDM2 and MDM4 are Therapeutic Vulnerabilities in Malignant Rhabdoid Tumors

Project description:Malignant rhabdoid tumors (MRT) are highly aggressive pediatric cancers that respond poorly to current therapies. We screened several MRT cell lines each with large-scale RNAi, CRISPR-Cas9, and small-molecule libraries to identify potential drug targets specific for these cancers. We discovered MDM2 and MDM4, the canonical negative regulators of p53, as significant vulnerabilities. Using two compounds currently in clinical development, idasanutlin and ATSP-7041, we show that MRT cells are more sensitive than other p53 wild-type cancer cell lines to MDM2 and dual MDM2/4 inhibition in vitro. These compounds cause significant upregulation of the p53 pathway in MRT cells, and sensitivity is ablated by CRISPR-Cas9-mediated inactivation of TP53. We show that loss of SMARCB1, a subunit of the SWI/SNF (BAF) complex mutated in nearly all MRT, sensitizes cells to MDM2 and MDM2/4 inhibition by enhancing p53-mediated apoptosis. Both MDM2 and MDM2/4 inhibition slowed MRT xenograft growth in vivo, with a five-day idasanutlin pulse causing marked regression of all xenografts including durable complete responses in 50% of mice. Together, these studies identify a genetic connection between mutations in the SWI/SNF chromatin-remodeling complex and the tumor suppressor gene p53, and provide preclinical evidence to support the targeting of MDM2 and MDM4 in this often-fatal pediatric cancer.

2019-02-04 | GSE124508 | GEO

Targeting MDM4/MDM2 binding interface for reactivation of p53 in cancer therapy

Project description:The aim of this experiment has been to investigate the transcriptional profile of HCT116 cells treated with Peptide-3 (Pep3) compared to untreated (NT), treated with solvent (DMSO) or with a mutated peptide (Pep3M) cells. Peptide-3 is a dodecapeptide able to interact with MDM2 at the levels of the interaction region of the MDM4 and MDM2 proteins, thereby interfering with the coopeartivy function of the proteins in the regulation of p53. This peptide is indeed able to specifically activate p53 and to cause apoptotis in different cancer cell lines and tumor growth inhibition in xenograft models.

2017-04-18 | GSE62855 | GEO

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [HCT116 microarray]

2015-12-31 | GSE73294 | GEO

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [ChIP-Seq]

2015-12-31 | GSE73293 | GEO