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.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Knockout of G protein β5 impairs brain development and causes multiple neurologic abnormalities in mice.
Specimen part
View SamplesConjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit tumorigenesis in a variety of cancer model systems. Based on previously well-documented anti-tumor activity of CLA in rodent models of breast cancer, a pilot study was initiated to examine the effect of dietary CLA in a well-established transgenic model of breast cancer. Western blots were performed for the detection of AKT, c-Src, ERK1/2, and Cdc24. CLA significantly increased tumor burden (p<0.1) independent of an increase in oncogenic signaling. Mammary gland whole mounts indicated a loss of mammary adipose and extensive epithelial expansion in CLA-treated animals. Microarray analysis indicated a significant reduction in cytoskeletal related genes with at least a two-fold decrease in five out of six CLA-fed animals compared to untreated controls. Reduction of Cdc42, a key regulator of cell adhesion and cytoskeletal arrangements, was confirmed at the protein level by western blot (p<0.01). These findings suggest that dietary CLA may advance the malignant phenotype by promoting a loss of cell polarity and adhesion in the mammary gland epithelium. This action may have serious clinical implications for a subset high-risk population and warrants further investigation.
Pilot study on the effects of dietary conjugated linoleic acid on tumorigenesis and gene expression in PyMT transgenic mice.
Sex, Age, Specimen part
View SamplesNlrc5 is encoding a Nod-like receptor protein NLRC5/NOD27. To check the involvement of Nlrc5 in antiviral response, we examined gene expression profile in wild-type and Nlrc5 knockout GM-CSF bone marrow macrophage with using microarrays.
NLRC5 deficiency does not influence cytokine induction by virus and bacteria infections.
Specimen part, Time
View SamplesRecurrent somatic mutations in TET2 and in other genes that regulate the epigenetic state have been identified in patients with myeloid malignancies and in other cancers. However, the in vivo effects of Tet2 loss have not been delineated. We report here that Tet2 loss leads to increased stem-cell self-renewal and to progressive stem cell expansion. Consistent with human mutational data, Tet2 loss leads to myeloproliferation in vivo, notable for splenomegaly and monocytic proliferation. In addition, haploinsufficiency for Tet2 confers increased self-renewal and myeloproliferation, suggesting that the monoallelic TET2 mutations found in most TET2-mutant leukemia patients contribute to myeloid transformation. This work demonstrates that absent or reduced Tet2 function leads to enhanced stem cell function in vivo and to myeloid transformation.
Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
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View SamplesRestricted feeding impacts the hepatic circadian clock of WT mice. Cry1, Cry2 double KO mice lack a circadian clock and are thus expected to show rhythmical gene expression in the liver. Imposing a temporally restricted feeding schedule on these mice shows how the hepatic circadian clock and rhythmic food intake regulate rhythmic transcription in parallel
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
No sample metadata fields
View SamplesTemporally restricted feeding is known to impact the circadian clock. This dataset shows the effects of temporally restricted feeding on the hepatic transcriptome.
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
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View SamplesTemporally restricted feeding has a profound effect on the circadian clock. Fasting and feeding paradigms are known to influence hepatic transcription. This dataset shows the dynamic effects of refeeding mice after a 24hour fasting period.
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
No sample metadata fields
View SamplesType I Interferons encompasses a large family of closely related cytokines comprising of at least 13 IFN- isotypes and single IFN-. Both IFN- and IFN- exert their activity through a common receptor IFNAR. Type I Interferons have broad regulatory effects and various subtypes of dendritic cells are influenced by this cytokines. In our study we asked question whether the low, constitutive levels of type I Interferons produced under steady state conditions are important for proper function of splenic conventional dendritic cells.
Absence of IFN-beta impairs antigen presentation capacity of splenic dendritic cells via down-regulation of heat shock protein 70.
Sex, Age, Specimen part
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