P27Kip1 regulates transcription of genes involved in tumorigenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA124183 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2011-12-01 | GSE20069 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE20064: Expression data from p27delta51 MEFs cells in quiescence GSE20068: p27 binds to promoters of multiple genes leading to their repression GSE27672: Expression data from p27WT, p27CK and KO MEFs cells in quiescence Refer to individual Series
2011-12-01 | E-GEOD-20069 | biostudies-arrayexpress
Project description:Nucleophosmin (NPM1) is a multifunctional histone chaperone that can activate acetylation-dependent transcription from chromatin templates in vitro. p300-mediated acetylation of NPM1 has been shown to further enhance its transcription activation potential. Acetylated and total NPM1 pools are increased in oral squamous cell carcinoma. However, the role of NPM1 or its acetylated form (AcNPM1) in transcriptional regulation in cells and oral tumorigenesis is not fully elucidated. Using ChIP-seq analyses, we provide the first genome-wide profile of AcNPM1 and show that AcNPM1 is enriched at transcriptional regulatory elements. AcNPM1 co-occupies marks of active transcription at promoters and DNase I hypersensitive sites at enhancers. In addition, using a high-throughput protein interaction profiling approach, we show that NPM1 interacts with RNA Pol II, general transcription factors, mediator subunits, histone acetyltransferase complexes, and chromatin remodelers. NPM1 histone chaperone activity also contributes to its transcription activation potential. Further, NPM1 depletion leads to decreased AcNPM1 occupancy and reduced expression of genes required for proliferative, migratory and invasive potential of oral cancer cells. NPM1 depletion also abrogates the growth of orthotopic tumors in mice. Collectively, these results establish that AcNPM1 functions as a coactivator during during RNA polymerase II-driven transcription and regulates the expression of genes that promote oral tumorigenesis.
| S-EPMC8852714 | biostudies-literature
Project description:The CDK inhibitor p27Kip1 is a critical regulator of cell cycle progression, but the mechanisms by which p27Kip1 controls cell proliferation in vivo are still not fully elucidated. We recently demonstrated that the microtubule destabilizing protein stathmin is a relevant p27Kip1binding partner involved in the regulation of cell motility. To get more insights into the in vivo significance of this interaction, we generated p27Kip1 and stathmin double knock out (DKO) mice. Interestingly, thorough characterization of DKO mice demonstrated that most of the phenotypes of p27Kip1 null mice linked to the hyperproliferative behavior, such as the increased body and organ weights, the outgrowth of the retina basal layer and the development of pituitary adenomas, were reverted by co-ablation of stathmin. In vivo analyses showed a reduced proliferation rate in DKO compared to p27kip1 null mice, linked, at molecular level, to decreased kinase activity of CDK4/6, rather than of CDK1 and CDK2. Gene expression profile analyses of mouse thymuses confirmed the phenotypes observed in vivo, demonstrating that DKO clustered with WT and not with p27KO thymuses. Taken together, the results demonstrate that stathmin cooperates with p27Kip1 to control the early phase of G1 to S phase transition and strongly suggest that this function has particular relevance in the contest of tumor progression.
2015-04-01 | GSE60078 | GEO
Project description:Loss of function of BRCA1 caused by inherited mutation and tissue-specific somatic mutation leads to breast and ovarian cancer. Nearly all BRCA1 germ-line mutations involve truncation or loss of the C-terminal BRCT transcriptional activation domain, suggesting that transcriptional regulation is a critical function of the wild-type gene. The purpose of this project was to determine whether there is a link between the role of BRCA1 in transcriptional regulation and its role in tumor suppression. We developed a cell line (in which BRCA1 can be induced) and used microarray analysis to compare transcription profiles of epithelial cells with low endogenous levels of BRCA1 vs. transcription profiles of cells with 2-4-fold higher induced levels of expression of BRCA1. At these levels of expression, BRCA1 did not induce apoptosis. Undirected cluster analysis of six paired experiments revealed 373 genes, the expression of which was altered significantly and consistently by BRCA1 induction. Expression of 62 genes was altered more than 2-fold. BRCA1-regulated genes associated with breast tumorigenesis included the estrogen-responsive genes MYC and cyclin D1, which are overexpressed in many breast tumors; STAT1 and JAK1, key components of the cytokine signal transduction pathway; the extracellular matrix protein laminin 3A; ID4, an inhibitor of DNA-binding transcriptional activators, which in turn negatively regulates BRCA1 expression; and the prohormone stanniocalcin, expression of which is lost in breast tumor cells. Coordinated expression of BRCA1 with ID4 and with stanniocalcin was confirmed in primary breast and ovarian tumors.
| S-EPMC124283 | biostudies-literature
Project description:The control of cell cycle progression mostly relays on the concerted activity of cyclins, CDKs and CDKs inhibitor. Recent data demonstrated that microRNAs, by regulating the expression of these proteins, contribute to the control of cell cycle progression. Here we provide evidences that the CDK inhibitor p27Kip1 directly regulates microRNAs stability thereby influencing cell cycle exit following contact inhibition. By the use of wild type and p27 knock-out cells we uncovered several microRNAs whose expression is linked to the cell cycle exit in a p27-dependent manner. By studying one of this microRNA, miR-223, we provide evidence that p27 is an RNA binding protein able to bind miR-223 to stabilize its expression. High miR-223 levels participate in the control of cell proliferation. Overall, we identify a previously completely unknown and conserved function of p27Kip1 that contributes to the proper regulation of cell cycle progression impinging on microRNA expression.
2015-12-31 | E-GEOD-45538 | biostudies-arrayexpress
Project description:The CDK inhibitor p27Kip1 is a critical regulator of cell cycle progression, but the mechanisms by which p27Kip1 controls cell proliferation in vivo are still not fully elucidated. We recently demonstrated that the microtubule destabilizing protein stathmin is a relevant p27Kip1binding partner involved in the regulation of cell motility. To get more insights into the in vivo significance of this interaction, we generated p27Kip1 and stathmin double knock out (DKO) mice. Interestingly, thorough characterization of DKO mice demonstrated that most of the phenotypes of p27Kip1 null mice linked to the hyperproliferative behavior, such as the increased body and organ weights, the outgrowth of the retina basal layer and the development of pituitary adenomas, were reverted by co-ablation of stathmin. In vivo analyses showed a reduced proliferation rate in DKO compared to p27kip1 null mice, linked, at molecular level, to decreased kinase activity of CDK4/6, rather than of CDK1 and CDK2. Gene expression profile analyses of mouse thymuses confirmed the phenotypes observed in vivo, demonstrating that DKO clustered with WT and not with p27KO thymuses. Taken together, the results demonstrate that stathmin cooperates with p27Kip1 to control the early phase of G1 to S phase transition and strongly suggest that this function has particular relevance in the contest of tumor progression. Four-conditions experiment (four different mouse genotypes), 6 biological replicates of wild type mouse thymus, 6 biological replicates of p27 knock-out mouse thymus, 6 biological replicates of stathmin knock-out mouse thymus, 6 biological replicates of double knock-out (p27 and stathmin) mouse thymus. Reference design: pool of RNAs derived from mouse fibroblasts of all the genotypes.Reference design;
2015-04-01 | E-GEOD-60078 | biostudies-arrayexpress
Project description:The integrated regulation of different intracellular signaling pathways is fundamental to ensure appropriate timing of cell division and, more in general, proper development of any living organism. Adopted mechanisms include the instauration of feedback regulations and/or to rely on a single molecule for the control of multiple processes. We now present evidences that in mammalian cells the CDK inhibitor p27kip1, by a CDK-independent and stathmin-dependent mechanism, is implicated in the control of the MAPK pathway, eventually influencing cell proliferation in vitro and mice growth in vivo. This p27kip1 activity regulates H-Ras driven transformation in mice and controls tumor progression in humans. Altogether, our work unveils a new mechanism that in mammalian cells contributes to proper regulation of cell proliferation and whose alteration may contribute to tumor onset and/or progression.
2015-11-02 | GSE31533 | GEO
Project description:Bidirectional communication between tumors and neurons has emerged as a key facet of the tumor microenvironment that drives malignancy. Another hallmark feature of cancer is epigenomic dysregulation, where alterations in gene expression influences cell states and interactions with the tumor microenvironment. Using the pediatric brain tumor ependymoma (EPN) as a model, we found that inhibition of histone serotonylation blocks EPN tumorigenesis and regulates expression of a core set of developmental transcription factors (TFs). High-throughput, in vivo screening of these TFs revealed that ETV5 promotes EPN tumorigenesis and functions by enhancing repressive chromatin states. Neuropeptide Y (NPY) is amongst the genes repressed by ETV5 and its overexpression suppresses EPN tumor progression and tumor-associated network hyperactivity via synaptic remodeling. Collectively, these studies identify histone serotonylation as a key driver of EPN tumorigenesis, while further revealing how neuronal signaling, neuro-epigenomics, and developmental programs are intertwined to drive malignancy in brain cancer.
2024-09-09 | PXD048170 | Pride
Project description:Histone serotonylation regulates ependymoma tumorigenesis through neurodevelopmental pathways
| PRJNA1031155 | ENA