Expression data from p27WT, p27CK and KO MEFs cells in quiescence
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE27672 | GEO | 2011/12/01
SECONDARY ACCESSION(S): PRJNA138185
REPOSITORIES: GEO
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Project description:Low levels of the cell cycle regulator p27Kip1 are associated with a worse outcome in many tumor types. We report here a new regulatory role of p27Kip1 as a transcriptional regulator. In association with transcriptional factors such as ETS and E2F4 and co-repressors like p130, HDACs and mSin3A, p27 binds to promoters of multiple genes leading to their repression. The p27-target genes participate in RNA processing, translation, respiration and cell cycle. Remarkably, p27-target genes are over-expressed in different human tumors in tight association with a poor clinical prognosis. We also observed a clear correlation between low levels of p27 and over-expression of p27-target genes in tumors. Overall, our findings indicate new tumor suppressor roles of p271 as a transcriptional regulator of genes relevant for oncogenesis. Samples from MEFs p27WT, p27CK and p27KO cells were analyzed
2011-12-01 | E-GEOD-27672 | biostudies-arrayexpress
Project description:Low levels of the cell cycle regulator p27Kip1 are associated with a worse outcome in many tumor types. We report here a new regulatory role of p27Kip1 as a transcriptional regulator. In association with transcriptional repressors such as p130, E2F4 and HDACs, p27 binds to promoters of multiple genes leading to their repression. The p27Kip1-target genes participate in RNA processing, translation, respiration and cell cycle. Remarkably, p27Kip1-target genes are over-expressed in different human tumors in tight association with a poor clinical prognosis. We also observed a clear correlation between low levels of p27Kip1 and over-expression of p27Kip1-target genes in tumors. Overall, our findings indicate new tumor suppressor roles of p27Kip1 as a transcriptional regulator of genes relevant for oncogenesis.
2011-12-01 | GSE20064 | GEO
Project description:Low levels of the cell cycle regulator p27Kip1 are associated with a worse outcome in many tumor types. We report here a new regulatory role of p27Kip1 as a transcriptional regulator. In association with transcriptional repressors such as p130, E2F4 and HDACs, p27 binds to promoters of multiple genes leading to their repression. The p27Kip1-target genes participate in RNA processing, translation, respiration and cell cycle. Remarkably, p27Kip1-target genes are over-expressed in different human tumors in tight association with a poor clinical prognosis. We also observed a clear correlation between low levels of p27Kip1 and over-expression of p27Kip1-target genes in tumors. Overall, our findings indicate new tumor suppressor roles of p27Kip1 as a transcriptional regulator of genes relevant for oncogenesis. Samples from MEFs p27delta51 and p27WT cells used as control were analyzed
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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;
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