Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA381790 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5419960.fastq.gz | Fastqsanger.gz | |||
| SRR5419970.fastq.gz | Fastqsanger.gz | |||
| SRR5419980.fastq.gz | Fastqsanger.gz | |||
| SRR5419961.fastq.gz | Fastqsanger.gz | |||
| SRR5419971.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 80 |
Similar Datasets
Project description:Dysregulation of kinase signaling pathways via mutations favors tumor cell survival and resistance to therapy and it is common in cancer. Here, we reveal a novel mechanism of post-translational regulation of kinase signaling and nuclear receptor activity via deubiquitination in acute leukemia. We observed that the ubiquitin specific protease 11 (USP11) is highly expressed in lymphoblastic leukemia and associates with poor prognosis in this disease. USP11 ablation inhibits leukemia growth in vitro and in vivo, sparing normal hematopoiesis and thymus development, suggesting that USP11 could be a therapeutic target in leukemia. USP11 forms a complex with USP7 to deubiquitinate the oncogenic lymphocyte cell-specific protein-tyrosine kinase (LCK). Deubiquitination of LCK controls its activity, thereby altering T cell receptor signaling. Impairment of LCK activity leads to increased expression of the glucocorticoid receptor transcript, culminating into transcriptional activation of pro-apoptotic target genes, and sensitizes cells to glucocorticoids in primary T cell leukemia patient samples. The transcriptional activation of pro-apoptotic target genes, such as BCL2L11, is orchestrated by the deubiquitinase activity and mediated via an increase in enhancer-promoter interaction intensity. Pharmacological inhibition of USP7 or genetic knockout of USP7 in combination treatment of glucocorticoid displayed improved anti-T-ALL efficacy in vivo. Our data unveil how dysregulated deubiquitination controls signaling pathways, leading to cancer cell survival and drug non-response, and suggest novel therapeutic combinations towards targeting leukemia.
2022-02-28 | MSV000088930 | MassIVE
Project description:Transcriptional deregulation plays a major role in acute myeloid leukemia, identification of epigenetic modifying enzymes essential for the maintenance of oncogenic transcription programs holds the key to better understanding the biology and designing effective therapeutic strategies for the disease. Here we provide experimental evidence showing the functional involvement and therapeutic potentials of targeting PRMT1 with H4R3 methyltransferase activity in various MLL and non-MLL leukemias. PRMT1 is necessary but not sufficient for leukemic transformation, which requires co-recruitment of KDM4C with H3K9 demethylase activity by chimeric transcription factors to mediate epigenetic reprogramming. Inhibition of KDM4C/PRMT1 suppresses transcription and transformation ability of MLL fusions and MOZ-TIF2, revealing a novel and targetable epigenetic circuitry mediated by PRMT1 and KDM4C in acute leukemia.
2016-01-14 | E-MTAB-3322 | biostudies-arrayexpress
Project description:Search for a novel therapeutic target in myeloid leukemia
| PRJNA316426 | ENA
Project description:Pathogenic variants in the ubiquitin-specific protease 7 (USP7) gene cause a neurodevelopmental disorder called Hao-Fountain syndrome. However, which of its pleiotropic substrates are relevant for neurodevelopment is undetermined. Here, we present a combination of quantitative proteomics, transcriptomics and epigenomics to define the USP7 regulatory circuitry during neurodifferentiation. USP7 activity is required for the transcriptional programs that direct differentiation of embryonic stem cells to neural stem cells, and neuronal differentiation of SHSY5Y neuroblastoma cells. USP7 controls the dosage of the Polycomb H2AK119ub1 ubiquitin ligases ncPRC1.1 and ncPRC1.6. Loss-of-function experiments revealed that BCOR-ncPRC1.1, but not ncPRC1.6, is a key effector of USP7-dependent neuronal differentiation. Indeed, BCOR-ncPRC1.1 mediates the majority of USP7-dependent gene regulation during this process. Besides providing a detailed map of the USP7 regulome during neurodifferentiation, our results suggest that USP7- and ncPRC1.1-associated neurodevelopmental disorders involve dysregulation of a common epigenetic network.
2025-09-08 | PXD051616 | Pride
Project description:Bladder cancer (BLCA) remains a highly lethal genitourinary malignancy with complex tumor biology and limited therapeutic strategies. This study investigates the oncogenic role of YKT6, a SNARE protein, in BLCA progression and molecular mechanisms. We demonstrate that YKT6 is significantly upregulated in BLCA tissues and cell lines, correlating with advanced tumor grade, aggressive histology, and poor patient prognosis. Comprehensive transcriptomic and functional analyses reveal that YKT6 promotes BLCA cell proliferation, migration, and metastasis both in vitro and in vivo. Mechanistically, YKT6 activates the Wnt/β-catenin signaling pathway through a novel mechanism involving USP7-mediated deubiquitination of β-catenin. By recruiting USP7, YKT6 inhibits β-catenin’s proteasomal degradation, thereby stabilizing the protein and driving nuclear accumulation. This stabilization leads to increased expression of oncogenic target genes and induces epithelial-mesenchymal transition (EMT). Pharmacological interventions demonstrated that Wnt signaling inhibition reverses YKT6-driven malignant effects, while pathway activation restores tumor progression in YKT6-silenced cells. USP7 knockdown abrogates YKT6-mediated β-catenin stabilization, confirming their functional interdependence. Clinically, the YKT6/USP7/β-catenin axis strongly correlates with poor prognosis, highlighting its potential as a diagnostic and therapeutic target. Our findings unveil YKT6 as a novel regulator of Wnt signaling through USP7-dependent deubiquitination, offering promising insights for precision BLCA therapy.
2025-11-27 | GSE293406 | GEO
Project description:Pathogenic variants of ubiquitin-specific protease 7 (USP7) cause the neurodevelopmental disorder Hao-Fountain syndrome. However, which of its pleiotropic substrates are relevant for neurodevelopment has remained unclear. Here, we present a combination of quantitative proteomics, transcriptomics and epigenomics to define the core USP7 circuitry during neurodifferentiation. USP7 activity is required for the transcriptional programs that direct the differentiation of human ESCs to neural stem cells, and neuronal differentiation of SHSY5Y neuroblastoma cells. In addition to other substrates, including TRIM27, USP7 controls the dosage of the Polycomb H2AK119ub1 ubiquitin ligases ncPRC1.1 and ncPRC1.6. We found that BCOR-ncPRC1.1, but not ncPRC1.6 or TRIM27, is a key effector of USP7-dependent neuronal differentiation. Indeed, BCOR-ncPRC1.1 mediates the majority of USP7-dependent gene regulation during this process. Besides providing a detailed map of the USP7 regulome during neuronal differentiation, our results suggest that Hao-Fountain syndrome and ncPRC1.1-associated neurodevelopmental disorders involve dysregulation of a shared epigenetic network.
2025-03-12 | GSE263489 | GEO
Project description:Pathogenic variants of ubiquitin-specific protease 7 (USP7) cause the neurodevelopmental disorder Hao-Fountain syndrome. However, which of its pleiotropic substrates are relevant for neurodevelopment has remained unclear. Here, we present a combination of quantitative proteomics, transcriptomics and epigenomics to define the core USP7 circuitry during neurodifferentiation. USP7 activity is required for the transcriptional programs that direct the differentiation of human ESCs to neural stem cells, and neuronal differentiation of SHSY5Y neuroblastoma cells. In addition to other substrates, including TRIM27, USP7 controls the dosage of the Polycomb H2AK119ub1 ubiquitin ligases ncPRC1.1 and ncPRC1.6. We found that BCOR-ncPRC1.1, but not ncPRC1.6 or TRIM27, is a key effector of USP7-dependent neuronal differentiation. Indeed, BCOR-ncPRC1.1 mediates the majority of USP7-dependent gene regulation during this process. Besides providing a detailed map of the USP7 regulome during neuronal differentiation, our results suggest that Hao-Fountain syndrome and ncPRC1.1-associated neurodevelopmental disorders involve dysregulation of a shared epigenetic network.
2025-03-12 | GSE263491 | GEO
Project description:Pathogenic variants of ubiquitin-specific protease 7 (USP7) cause the neurodevelopmental disorder Hao-Fountain syndrome. However, which of its pleiotropic substrates are relevant for neurodevelopment has remained unclear. Here, we present a combination of quantitative proteomics, transcriptomics and epigenomics to define the core USP7 circuitry during neurodifferentiation. USP7 activity is required for the transcriptional programs that direct the differentiation of human ESCs to neural stem cells, and neuronal differentiation of SHSY5Y neuroblastoma cells. In addition to other substrates, including TRIM27, USP7 controls the dosage of the Polycomb H2AK119ub1 ubiquitin ligases ncPRC1.1 and ncPRC1.6. We found that BCOR-ncPRC1.1, but not ncPRC1.6 or TRIM27, is a key effector of USP7-dependent neuronal differentiation. Indeed, BCOR-ncPRC1.1 mediates the majority of USP7-dependent gene regulation during this process. Besides providing a detailed map of the USP7 regulome during neuronal differentiation, our results suggest that Hao-Fountain syndrome and ncPRC1.1-associated neurodevelopmental disorders involve dysregulation of a shared epigenetic network.
2025-03-12 | GSE263490 | GEO
Project description:T-cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling. In this study we chemically inhibited the deubiquinating enzyme USP7 and assayed for gene expression changes. This piece of data was further integrated to epigenetic changes using ChIP-Sequencing analysis of H3K27me3, H2AUb, H2BUb, H3K27Ac and H3K79me2 upon inhibition of USP7. These results coupled helped to determine the role of USP7 in stabilizing and promoting T-ALL leukemia. We also compared the gene expression and epigenetic changes of USP7 inhibition with inhibition of NOTCH1 pathway and JMJD3.
2018-11-01 | GSE97435 | GEO
Project description:Modification by ubiquitin controls the stability of most cellular proteins, and deregulation contributes to a variety of human diseases such as cancer. Deubiquitinases (DUBs) remove ubiquitin from proteins, and the inhibition of DUBs has been recognized as a therapeutic strategy to induce degradation of specific proteins, a concept extendable to ‘undruggable’ targets such as transcription factors. However, this potential has remained untapped; specific small molecule inhibitors for DUBs are scarce and insights into mechanisms of action are limited. Ubiquitin specific protease (USP) 7 stabilises the oncogenic E3 ligase MDM2 that destabilises the tumour suppressor p53 and inhibition of USP7 results in MDM2 degradation and p53 re-activation in a variety of cancers. We here present two small molecule inhibitors, FT671 and FT827, that inhibit USP7 with nanomolar affinity and display exquisite specificity towards USP7 in vitro and in cells. USP7-inhibitor co-crystal structures reveal that both compounds target the auto-inhibited apo-form of USP7 and bind in proximity to the misaligned catalytic triad in a dynamic hydrophobic pocket that serves as the binding site for the ubiquitin C-terminus. The unique auto-inhibited conformation of apo USP7 differs from other USP DUBs, explaining compound selectivity. Consistent with USP7 target engagement in cells, FT671 destabilises MDM2, stabilises p53 and results in transcription of p53 target genes, induction of the tumour suppressor p21, and tumour growth inhibition in vivo.
2018-04-05 | PXD006418 | Pride