In order to assess the physiological role of Cop1 in vivo we generated mice that do no longer express the protein. Cop1KO mice die at around E10.5 of embryonic development. In order to gain insights into the molecular mechanisms that cause the embryonic death we compared the genome-wide gene expression profile of E9.5 wild-tytpe and Cop1-null embryos. The data do not support a role for Cop1 in the regulation of the p53 pathway in vivo and highlight a role for Cop1 in cardiovascular development and/or angiogenesis. The abstract of the associated publication is as follows:Biochemical data have suggested conflicting roles for the E3 ubiquitin ligase Cop1 in tumourigenesis. Here we present the first in vivo investigation of the role of Cop1 in cancer aetiology. We used an innovative genetic approach to generate an allelic series of Cop1 and show that Cop1 hypomorphic mice spontaneously develop malignancy at a high frequency in their first year of life and are highly susceptible to radiation-induced lymphomagenesis. Biochemically, we show that Cop1 regulates c-Jun oncoprotein stability and modulates c-Jun/AP1 transcriptional activity in vivo. Cop1-deficiency stimulates cell proliferation in a c-Jun-dependent manner. We conclude that Cop1 is a tumour suppressor that antagonizes c-Jun oncogenic activity in vivo.
Cop1 constitutively regulates c-Jun protein stability and functions as a tumor suppressor in mice.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging.
Age, Specimen part
View SamplesInsulin-dependent diabetes is a complex multifactorial disorder characterized by
Identification of proliferative and mature β-cells in the islets of Langerhans.
Sex, Specimen part
View SamplesGene expression profiling of the medial (MGE), lateral (LGE) and caudal (CGE) ganglionic eminence, and cerebral cortex (CTX) at various embryonic stages (E12.5, E14 and E16).
Comprehensive spatiotemporal transcriptomic analyses of the ganglionic eminences demonstrate the uniqueness of its caudal subdivision.
Sex, Specimen part
View SamplesExpression in GFP vs. GFP/hTERT transduced CD8 T Lymphocytes from Healty Donors (HD) 1 and 2 at early and late passages. Using CD8+ T lymphocyte clones over-expressing telomerase we investigated the molecular mechanisms that regulate T cell proliferation. Transduction and subcloning procedures were performed on CD8 + naive T-cell clones isolated from two different healthy individuals aged between 30 to 35 years (HD1 and HD2). T-cell cloneswere transduced to express hTERT/GFP or GFP alone.
Mechanisms regulating the proliferative potential of human CD8+ T lymphocytes overexpressing telomerase.
No sample metadata fields
View SamplesUsing CD8+ T lymphocyte clones over-expressing telomerase weinvestigated the molecular mechanisms that regulate T cell proliferation. Transduction and subcloning procedures were performed on CD8 + naive T-cell clones isolated from two different healthy individuals aged between 30 to 35 years (HD1 and HD2). T-cell cloneswere transduced to express hTERT/GFP or GFP alone. HD2 was profiled on U133Plus 2.0 and submitted as a separate GEO series.
Mechanisms regulating the proliferative potential of human CD8+ T lymphocytes overexpressing telomerase.
No sample metadata fields
View SamplesUsing CD8+ T lymphocyte clones over-expressing telomerase weinvestigated the molecular mechanisms that regulate T cell proliferation. Transduction and subcloning procedures were performed on CD8 + naive T-cell clones isolated from two different healthy individuals aged between 30 to 35 years (HD1 and HD2). T-cell cloneswere transduced to express hTERT/GFP or GFP alone. HD1 was profiled on U133A and submitted as a separate GEO series.
Mechanisms regulating the proliferative potential of human CD8+ T lymphocytes overexpressing telomerase.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Diurnal regulation of RNA polymerase III transcription is under the control of both the feeding-fasting response and the circadian clock.
Specimen part
View SamplesRNA polymerase III (pol III) synthesizes short non-coding RNAs, many of which, including tRNAs, Rpph1 RNA, Rn5s rRNA, and Rmrp RNA, are essential for translation. Accordingly, pol III activity is tightly regulated with cell growth and proliferation by factors such as MYC, RB1, TRP53, and MAF1. MAF1 is a repressor of pol III transcription whose activity is controlled by phosphorylation; in particular, it is inactivated through phosphorylation by mTORC1 kinase, a sensor of nutrient availability. Pol III regulation is thus sensitive to environmental cues, yet a diurnal profile of pol III transcription activity is so far lacking. Here we document pol III occupancy of its target genes in mouse liver during the diurnal cycle and show that pol III occupancy rises before the onset of the night, stays high during the night, when mice normally ingest food and when translation is increased, and decreases in daytime. By comparing diurnal pol III occupancy in wild-type mice, arrhythmic mice owing to inactivation of the Arntl gene, mice fed at regular intervals during both night and day, and mice lacking the Maf1 gene, we show that whereas higher pol III occupancy during the night reflects a MAF1-dependent response to feeding, the rise of pol III occupancy before the onset of the night reflects a circadian clock-dependent response. Thus, pol III transcription during the diurnal cycle is regulated both in response to nutrients and by the circadian clock, which allows anticipatory pol III transcription.
Diurnal regulation of RNA polymerase III transcription is under the control of both the feeding-fasting response and the circadian clock.
Specimen part
View SamplesReexpression of microRNAs miR-15a/16-1 in a cell line deficient for these miRs (homozygous deletion of chromosomal region 13q14) results in the downregulation of certain mRNAs.
The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia.
Cell line
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