Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-40513
PROVIDER: PRJNA174203 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Continuous requirement for the T cell receptor for regulatory T cell function
2015-08-05 | E-GEOD-61077 | ExpressionAtlas
Project description:Cyclin C was cloned as a growth-promoting G1 cyclin1,2, and several studies postulated a role for cyclin C in driving cell proliferation3-8 . Moreover, cyclin C, together with its kinase partner, the cyclin-dependent kinase CDK8, is believed to represent an essential component of basal transcriptional machinery where it globally represses gene expression9-13. However, the function of cyclin C in vivo has never been addressed. Here we show that in the living organism cyclin C acts as a haploinsufficient tumor suppressor, through its function of controlling Notch1 oncogene levels. Cyclin C activates an “orphan” CDK19 kinase14, as well as CDK8 and CDK3. These cyclin C-CDK complexes phosphorylate Notch1 intracellular domain (ICN1), which allows binding of ICN1 to Fbw7 and triggers ICN1 polyubiquitination. Genetic ablation of cyclin C blocks ICN1 phosphorylation, disrupts Fbw7 binding, and decreases ICN1 ubiquitination in vivo, thereby strongly elevating ICN1 levels in several compartments of cyclin C knockout mice. Cyclin C was cloned as a growth-promoting G1 cyclin1,2, and several studies postulated a role for cyclin C in driving cell proliferation3-8 . Moreover, cyclin C, together with its kinase partner, the cyclin-dependent kinase CDK8, is believed to represent an essential component of basal transcriptional machinery where it globally represses gene expression9-13. However, the function of cyclin C in vivo has never been addressed. Here we show that in the living organism cyclin C acts as a haploinsufficient tumor suppressor, through its function of controlling Notch1 oncogene levels. Cyclin C activates an “orphan” CDK19 kinase14, as well as CDK8 and CDK3. These cyclin C-CDK complexes phosphorylate Notch1 intracellular domain (ICN1), which allows binding of ICN1 to Fbw7 and triggers ICN1 polyubiquitination. Genetic ablation of cyclin C blocks ICN1 phosphorylation, disrupts Fbw7 binding, and decreases ICN1 ubiquitination in vivo, thereby strongly elevating ICN1 levels in several compartments of cyclin C knockout mice.
2017-03-29 | MSV000080728 | MassIVE
Project description:Purpose: To gain insights into the activity of Cyclin D1 in tumor maintenance, we developed a specific RNAi strategy to knock down its expression and analyze the outcome on gene expression profile of the entire tumor. Method: MMTV-ErbB2 or RAS/DNP53-driven tumor mRNA profiles were generated by RNA-Sequencing. Results: Cyclin D1 knock down in RAS-G12V or MMTV-ErbB2-driven tumors leads to expression change of genes involved in developmental processes, but no change in FAS or FASL levels.
2021-03-20 | GSE112106 | GEO
Project description:Cyclin C was cloned as a growth-promoting G1 cyclin, and several studies postulated a role for cyclin C in driving cell proliferation. Moreover, cyclin C, together with its kinase partner, the cyclin-dependent kinase CDK8, is believed to represent an essential component of basal transcriptional machinery where it globally represses gene expression. However, the function of cyclin C in vivo has never been addressed. Here we show that in the living organism cyclin C acts as a haploinsufficient tumor suppressor, through its function of controlling Notch1 oncogene levels. Cyclin C activates an M-bM-^@M-^\orphanM-bM-^@M-^] CDK19 kinase, as well as CDK8 and CDK3. These cyclin C-CDK complexes phosphorylate Notch1 intracellular domain (ICN1), which allows binding of ICN1 to Fbw7 and triggers ICN1 polyubiquitination. Genetic ablation of cyclin C blocks ICN1 phosphorylation, disrupts Fbw7 binding, and decreases ICN1 ubiquitination in vivo, thereby strongly elevating ICN1 levels in several compartments of cyclin C knockout mice. Ablation of cyclin C, or cyclin C heterozygosity collaborate with other oncogenic lesions and accelerate development of T-cell acute lymphoblastic leukemia (T-ALL) in cyclin Cdeficient mice. Furthermore, the locus encoding cyclin C is heterozygously deleted in a significant fraction of human T-ALL, and these tumors express reduced cyclin C levels. In addition, we describe point mutations in human T-ALL tumors that render cyclin C-CDK unable to phosphorylate ICN1. These studies reveal that in sharp contrast to all other cyclin proteins, cyclin C functions as a growth-suppressor in vivo, and suggest that human tumor cells develop different strategies to evade cyclin C inhibitory function. Comparison of wild-type mouse embryonic fibroblasts (n=3 biological replicates) versus cyclin C knockout MEFs (n=3), wild-type mouse embryonic stem cells (n=3) versus cyclin C knockout ESC (n=3), wild-type mouse embryonic brain (n=3) versus cyclin C knockout embryonic brain (n=3)
2014-09-02 | E-GEOD-58712 | biostudies-arrayexpress
Project description:Predominant Requirement of Mitochondrial Transcriptional Factor A in Tissue-resident Regulatory T cell Maintenance and Function
| PRJNA545234 | ENA
Project description:Cyclin C was cloned as a growth-promoting G1 cyclin1,2, and several studies postulated a role for cyclin C in driving cell proliferation3-8 . Moreover, cyclin C, together with its kinase partner, the cyclin-dependent kinase CDK8, is believed to represent an essential component of basal transcriptional machinery where it globally represses gene expression9-13. However, the function of cyclin C in vivo has never been addressed. Here we show that in the living organism cyclin C acts as a haploinsufficient tumor suppressor, through its function of controlling Notch1 oncogene levels. Cyclin C activates an “orphan” CDK19 kinase14, as well as CDK8 and CDK3. These cyclin C-CDK complexes phosphorylate Notch1 intracellular domain (ICN1), which allows binding of ICN1 to Fbw7 and triggers ICN1 polyubiquitination. Genetic ablation of cyclin C blocks ICN1 phosphorylation, disrupts Fbw7 binding, and decreases ICN1 ubiquitination in vivo, thereby strongly elevating ICN1 levels in several compartments of cyclin C knockout mice. Cyclin C was cloned as a growth-promoting G1 cyclin1,2, and several studies postulated a role for cyclin C in driving cell proliferation3-8 . Moreover, cyclin C, together with its kinase partner, the cyclin-dependent kinase CDK8, is believed to represent an essential component of basal transcriptional machinery where it globally represses gene expression9-13. However, the function of cyclin C in vivo has never been addressed. Here we show that in the living organism cyclin C acts as a haploinsufficient tumor suppressor, through its function of controlling Notch1 oncogene levels. Cyclin C activates an “orphan” CDK19 kinase14, as well as CDK8 and CDK3. These cyclin C-CDK complexes phosphorylate Notch1 intracellular domain (ICN1), which allows binding of ICN1 to Fbw7 and triggers ICN1 polyubiquitination. Genetic ablation of cyclin C blocks ICN1 phosphorylation, disrupts Fbw7 binding, and decreases ICN1 ubiquitination in vivo, thereby strongly elevating ICN1 levels in several compartments of cyclin C knockout mice.
2016-07-06 | PXD001237 | Pride
Project description:This study was designed to examine the requirement for the p63 transcription factor in Squamous Cell Carcinoma (SCC) tumor maintenance in an in vivo murine system. A tamoxifen-inducible Keratin 14-driven Cre recombinase transgene was used to conditionally excise p63 in advanced murine SCC tumors. These data show the context-dependent regulation of p63 target genes in cancer. Total RNA from murine Squamous Cell Carcinoma tumors was examined 1-3 days following genomic excision of TP63 in Keratin 14-expressing tumor cells.
2013-08-06 | E-GEOD-45929 | biostudies-arrayexpress
Project description:Cyclin D1b is a splice variant of the cell cycle regulator Cyclin D1 and is known to harbor divergent and highly oncogenic functions in human disease. While Cyclin D1b is induced during disease progression in many cancer types, the mechanisms underlying Cyclin D1b function remain poorly understood. Herein, models of human disease were utilized to resolve the downstream pathways requisite for the pro-tumorigenic functions of Cyclin D1b. Specifically, it was shown that Cyclin D1b modulates the expression of a large transcriptional network that cooperates with AR signaling to enhance tumor cell growth and invasive potential. Notably, Cyclin D1b promoted AR-dependent activation of genes associated with metastatic phenotypes. Further exploration determined that transcriptional induction of SNAI2 (Slug) was essential for Cyclin D1b- mediated proliferative and invasive properties, implicating Slug as a critical driver of disease progression. Importantly, Cyclin D1b expression highly correlated with that of Slug in clinical samples of advanced disease. Further, in vivo analyses provided strong evidence that Slug enhances both tumor growth and homing to distal soft tissues. Collectively, these findings reveal the underpinning mechanisms behind the pro-tumorigenic functions of Cyclin D1b, and demonstrate that the convergence of the Cyclin D1b-AR and Slug pathways results in the activation of processes critical for the promotion of lethal tumor phenotypes. Analysis of transcriptomes under the control of individual D-type cyclin isoforms in the hormone dependent prostate cancer cell line LNCaP in the presence and absence of androgen. LNCaP cells cultured in charcoal dextran treated media were transduced with virus encoding Cyclin D1a, Cyclin D1b, or control GFP for 24 hours in biological triplicate. Cells were then stimulated with either 1nM DHT or 0.01% EtOH (vehicle control) for 16 hours and harvested for RNA
2013-03-31 | E-GEOD-40794 | biostudies-arrayexpress
Project description:Impaired control of the G1/S checkpoint allows initiation of DNA replication under non-permissive conditions. Unscheduled S-phase entry is associated with DNA replication stress, demanding for other checkpoints or cellular pathways to maintain proliferation. Here, we uncovered a requirement for ADARp150 to sustain proliferation of G1/S-checkpoint-defective cells under growth-restricting conditions. Besides its well-established mRNA editing function in inversely oriented short interspersed nuclear elements (SINEs), we found ADARp150 to exert a critical function in mitosis. ADARp150 depletion resulted in tetraploidization, impeding cell proliferation in mitogen-deprived conditions. Mechanistically we show that ADAR1 depletion induced aberrant expression of Cyclin B3, which was causative for mitotic failure and whole-genome duplication. Finally, we find that also in vivo ADAR1-depletion-provoked tetraploidization hampers tumor outgrowth.
2024-10-10 | GSE262277 | GEO
Project description:Purpose: To gain insights into the activity of Cyclin D1 in tumor maintenance, we developed a cancer cell-specific RNAi strategy to knock down its expression and analyze the outcome on gene expression profile of the entire tumor. Method: RAS/DNP53-driven tumor mRNA profiles were generated by RNA-Sequencing. Reads from RNA-Seq samples were mapped to the Mus musculus reference genome (MGSCv37) using Bowtie and TopHat. Transcript abundance and differential expression were called by Cufflinks. Results: Cyclin D1 knock down in RAS-G12V or MMTV-ErbB2-driven tumors leads to expression change of genes involved in developmental processes, but no significant change in apoptotic genes was recorded among the samples.
2020-04-11 | GSE63578 | GEO