The restoration of catalytic activity to mutant enzymes by small molecules is well-established for in vitro systems. Here we show that the protein tyrosine kinase Src R388A mutant can be rescued in live cells using the small molecule imidazole. Cellular rescue of a v-Src homolog was rapid and reversible and conferred predicted oncogenic properties. Using chemical rescue in combination with mass spectrometry, six known Src kinase substrates were confirmed, and several new protein targets identified. Chemical rescue data suggests that c-Src is active under basal conditions. Rescue of R388A c-Src also allowed contributions of Src to the MAP kinase pathway to be clarified. This chemical rescue approach is likely to be of broad utility in cell signaling.
Chemical rescue of a mutant enzyme in living cells.
No sample metadata fields
View SamplesBACKGROUND: p53 is an important tumor suppressor with a known role in the later stages of colorectal cancer, but its relevance to the early stages of neoplastic initiation remains somewhat unclear. Although p53-dependent regulation of Wnt signalling activity is known to occur, the importance of these regulatory mechanisms during the early stages of intestinal neoplasia has not been demonstrated.
A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine.
Specimen part
View SamplesBackground: It has been shown previously that administration of Francisella tularensis (Ft) LVS lipopolysaccharide (LPS) protects mice against subsequent challenge with Ft LVS and blunts the pro-inflammatory cytokine response.
Modulation of hepatic PPAR expression during Ft LVS LPS-induced protection from Francisella tularensis LVS infection.
Age, Specimen part
View SamplesGene expression profiling was carried out on splenocyte mRNA samples collected from 10 animals subject to repeated social threat (pooled into 2 groups of 5) and 10 animals subject to non-threatening control conditions (pooled into 2 groups of 5). The primary research question is whether gene expression differs in CD11b+ splenocytes from animals exposed to social threat vs non-threatening control conditions.
Computational identification of gene-social environment interaction at the human IL6 locus.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Foxl2 functions in sex determination and histogenesis throughout mouse ovary development.
Sex, Subject
View SamplesComparison of Foxl2-null ovaries to wildtype ovaries, ovaries lacking Wnt4 or Kit, or testes, throughout mouse development.
Foxl2 functions in sex determination and histogenesis throughout mouse ovary development.
No sample metadata fields
View SamplesWe examined the transcriptional function of cyclin D1 in mouse development using two approaches. First, we queried association of cyclin D1 with the genome of E14.5 mouse embryos using ChIP-on-chip approach. We observed binding of cyclin D1 to several promoter regions. Second, we compared gene expression profiles between wild-type and cyclin D1-null retinas. We observed several transcripts with altered levels in cyclin D1-null organs.
Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen.
No sample metadata fields
View SamplesCyclin D1 belongs to the core cell cycle machinery1, and it is frequently overexpressed in human cancers2. The full repertoire of cyclin D1 functions in normal development and in cancer cells is currently unknown. To address this question, here we introduce a novel approach that allows one to determine the set of cyclin D1-interacting proteins (D1 interactome) and cyclin D1-bound genomic fragments (D1 cistrome) in essentially any mouse organ, at any point of development or at any stage of cancer progression. Using this approach, we detected several novel tissue-specific interactors of cyclin D1. A significant number of these partners represent proteins involved in transcription. We show, using genome-wide location analysis3, that cyclin D1 occupies promoters of a very large number of genes in the developing mouse, where it binds in close proximity to transcription start sites. Bioinformatics analyses of cyclin D1-bound genomic segments in the developing embryo revealed DNA recognition sequences for several transcription factors. By querying SAGE libraries4, promoter CpG content5 and gene expression profiles of cyclin D1-null organs, we demonstrate that cyclin D1 binds promoters of highly expressed genes, and that it functions to activate or to repress gene expression in vivo. Analyses of cyclin D1 transcriptional targets reveal that cyclin D1 contributes to cell proliferation by upregulating genes required for S-phase entry and progression. Hence, cyclin D1 plays a broad transcriptional regulatory function in vivo during normal mouse development.
Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dynamic regulatory network controlling TH17 cell differentiation.
Specimen part, Treatment
View SamplesPurpose: We generated extensive transcriptional and proteomic profiles from a Her2-driven mouse model of breast cancer that closely recapitulates human breast cancer. This report makes these data publicly available in raw and processed forms, as a resource to the community. Importantly, we previously made biospecimens from this same mouse model freely available through a sample repository, so researchers can obtain samples to test biological hypotheses without the need of breeding animals and collecting biospecimens.
Proteome and transcriptome profiles of a Her2/Neu-driven mouse model of breast cancer.
Sex, Specimen part
View Samples