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: Not available
| 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: Not available
| 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 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: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: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