Lambert_SAINT2096_rBRD4_domain_pulldown_P82_VS5
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ Orbitrap Elite
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Anne-Claude Gingras
PROVIDER: MSV000080986 | MassIVE | Mon Apr 24 19:46:00 BST 2017
SECONDARY ACCESSION(S): PXD006370
REPOSITORIES: MassIVE
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Project description:This submission contains the mass spectrometry files for the manuscript by Lambert, Picaud et al. that describes the characterization of interactome changes induced by JQ1 on the BET proteins. More precisely, files used in the SAINT express task 2086 are in this dataset. The BioID experiments of BRD3, WT and mutants, treated with JQ1 and acquired on TripleTOF 5600 spectrometers are found here. See the README file within "Materials and Methods" and the accompanying files for a complete description of MS data generated.
2017-04-25 | MSV000081001 | MassIVE
Project description:This submission contains the mass spectrometry files for the manuscript by Lambert, Picaud et al. that describes the characterization of interactome changes induced by JQ1 on the BET proteins. More precisely, files used in the SAINT express task 2841 are in this dataset. The AP-MS experiments using 3xFLAG tagged BET proteins lacking their ET domain acquired on TripleTOF 5600 mass spectrometers are found here. See the README file within "Materials and Methods" and the accompanying files for a complete description of MS data generated.
2017-04-24 | MSV000080988 | MassIVE
Project description:This submission contains the mass spectrometry files for the manuscript by Lambert, Picaud et al. that describes the characterization of interactome changes induced by JQ1 on the BET proteins. More precisely, files used in the SAINT express task 2307 are in this dataset. The AP-MS experiments involving a JQ1 time-course for 3xFLAG tagged BET proteins acquired on TripleTOF 5600 spectrometers are found here; please note that the SWATH/DIA files were used for quantification (MSPLIT-DIA) while the DDA files were used for library construction. See the README file within "Materials and Methods" and the accompanying files for a complete description of MS data generated.
2017-04-25 | MSV000081006 | MassIVE
Project description:This submission contains the mass spectrometry files for the manuscript by Lambert, Picaud et al. that describes the characterization of interactome changes induced by JQ1 on the BET proteins. This submission contains 16 files associated with endogenous IP-MS analysis of BRD2, BRD3 and BRD4 (IgG was used as a negative control) from K562 cells treated with (+)-JQ1 or DMSO for 1 h; biological duplicate analyses were performed. Sample were analysed on a TripleTOF 5600 spectrometer; please note that the SWATH/DIA files were used for quantification (MSPLIT-DIA) while the DDA files were used for library construction. See the README file within "Materials and Methods" and the accompanying files for a complete description of MS data generated.
2018-08-28 | MSV000082859 | MassIVE
Project description:This submission contains the mass spectrometry files for the manuscript by Lambert, Picaud et al. that describes the characterization of interactome changes induced by JQ1 on the BET proteins. This submission contains 16 files associated with endogenous IP-MS analysis of BRD2, BRD3 and BRD4 (IgG was used as a negative control) from Flp-In T-REx HEK293 cells treated with (+)-JQ1 or DMSO for 1 h; biological duplicate analyses were performed. Sample were analysed on a TripleTOF 5600 spectrometer; please note that the SWATH/DIA files were used for quantification (MSPLIT-DIA) while the DDA files were used for library construction. See the README file within "Materials and Methods" and the accompanying files for a complete description of MS data generated.
2018-08-28 | MSV000082857 | MassIVE
Project description:This submission contains the mass spectrometry files for the manuscript by Lambert, Picaud et al. that describes the functional characterization of the human acetyl lysine machinery. More precisely, files used in the SAINT express task 2437 are in this dataset. The AP-MS experiments using 3xFLAG tagged BRD9 fragments acquired on TripleTOF 5600 mass spectrometers are found here. See the README file within "Materials and Methods" and the accompanying files for a complete description of MS data generated.
2017-04-24 | MSV000080981 | MassIVE
Project description:Triple negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. Here we report the preferential and high sensitivity of TNBCs to BET bromodomain inhibitors such as JQ1 manifested by cell cycle arrest in early G1, apoptosis, and induction of markers of luminal epithelial differentiation in vitro and in vivo. The sensitivity of TNBC and other tumor types to BET inhibition establishes a rationale for clinical investigation, and a motivation to understand mechanisms of resistance. After engendering acquired resistance to BET inhibition in previously sensitive TNBCs, we utilized integrative approaches to identify a unique mechanism of epigenomic resistance to this epigenetic therapy. Resistant cells remain dependent on BRD4, confirmed by RNA interference. However, TNBC cells adapt to BET bromodomain inhibition by re-recruitment of unmutated BRD4 to super-enhancers, now in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify hyper-phosphorylation of BRD4 and strong association with MED1. Together, these studies provide a rationale for BET inhibition in TNBC and argue for combination strategies to anticipate clinical drug resistance. ChIP-seq in parental and JQ1 resistant triple negative breast cancer (TNBC) in response to DMSO or JQ1 treatment
2016-01-07 | E-GEOD-63581 | biostudies-arrayexpress
Project description:Triple negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. Here we report the preferential and high sensitivity of TNBCs to BET bromodomain inhibitors such as JQ1 manifested by cell cycle arrest in early G1, apoptosis, and induction of markers of luminal epithelial differentiation in vitro and in vivo. The sensitivity of TNBC and other tumor types to BET inhibition establishes a rationale for clinical investigation, and a motivation to understand mechanisms of resistance. After engendering acquired resistance to BET inhibition in previously sensitive TNBCs, we utilized integrative approaches to identify a unique mechanism of epigenomic resistance to this epigenetic therapy. Resistant cells remain dependent on BRD4, confirmed by RNA interference. However, TNBC cells adapt to BET bromodomain inhibition by re-recruitment of unmutated BRD4 to super-enhancers, now in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify hyper-phosphorylation of BRD4 and strong association with MED1. Together, these studies provide a rationale for BET inhibition in TNBC and argue for combination strategies to anticipate clinical drug resistance. RNA-Seq in parental and JQ1 resistant triple negative breast cancer (TNBC) in response to DMSO or JQ1 treatment over time
2016-01-07 | E-GEOD-63582 | biostudies-arrayexpress
Project description:Background: Neurofibromatosis type 2 (NF2) is an autosomal dominant genetic disease characterized by the development of multiple Schwannomas, usually occurring on both VIIIth (vestibular) cranial nerves. Bromodomain and extra-terminal domain (BET) proteins regulate gene transcription and their activity is required in a variety of cancers including malignant peripheral nerve sheath tumors (MPNST). The use of BET inhibitors as a therapeutic option to treat NF2 schwannomas has not been explored and is the focus of this study. Methods: A panel of normal and NF2-null Schwann cell and schwannoma cell lines were used to characterize the impact of the BET inhibitor JQ1 in vitro and in vivo. The mechanism of action was explored by chromatin immunoprecipitation (ChIP) of the BET BRD4, phospho-kinase arrays and immunohistochemistry of BRD4 in human vestibular schwannomas. Results: JQ1 inhibited the proliferation of NF2-null schwannoma and Schwann cell lines in vitro and in vivo. Further, loss of NF2 by CRISPR deletion or siRNA knockdown increased the sensitivity of cells to JQ1. Knock-down experiments identified BRD4 as the BET family member mediating the majority of JQ1 effects on cell proliferation. Immunohistochemistry demonstrated elevated levels of BRD4 protein in human vestibular schwannomas. BRD4 ChIP experiments identified the small G-protein Rac1 and PI3K signaling pathways as sensitive to JQ1. Conclusions: NF2 deficient Schwann cell and schwannoma cells are sensitive to BET inhibition, primarily mediated by BRD4, which is overexpressed in human vestibular schwannomas. BRD4 regulates Rac/Ras and PI3K signaling pathways and inhibition of these pathways by JQ1 impedes NF2 Schwannoma growth. These findings implicate BET inhibition as a therapeutic option for NF2-deficient schwannomas.
2022-08-02 | GSE167560 | GEO
Project description:Men who develop metastatic castration-resistant prostate cancer (CRPC) invariably succumb to the disease. The development and progression to CRPC following androgen ablation therapy is predominantly driven by unregulated androgen receptor (AR) signaling1-3. Despite the success of recently approved therapies targeting AR signaling such as abiraterone4-6 and second generation anti-androgens MDV3100 (enzalutamide)7,8, durable responses are limited, presumably due to acquired resistance. Recently JQ1 and I-BET, two selective small molecule inhibitors that target the amino-terminal bromodomains of BRD4, have been shown to exhibit antiproliferative effects in a range of malignancies9-12. Here we show that AR signaling-competent CRPC cell lines are preferentially sensitive to BET bromodomain inhibition. BRD4 physically interacts with the N-terminal domain of AR and can be disrupted by JQ111,13. Like the direct AR antagonist, MDV3100, JQ1 disrupted AR recruitment to target gene loci. In contrast to MDV3100, JQ1 functions downstream of AR, and more potently abrogated BRD4 localization to AR target loci and AR mediated gene transcription including induction of TMPRSS2-ERG and its oncogenic activity. In vivo, BET bromodomain inhibition was more efficacious than direct AR antagonism in CRPC xenograft models. Taken together, these studies provide a novel epigenetic approach for the concerted blockade of oncogenic drivers in advanced prostate cancer. Examination of AR, BRD2, BRD3, BRD4, ERG, RNA Pol II and H3K27ac in prostate cancer cells with respect to BET inhibitors
2014-04-25 | E-GEOD-55062 | biostudies-arrayexpress