Post-translational regulation of the MYC Transcription Factor (TF), including its phosphorylation and ubiquitination, plays an important role in determining cell proliferation and apoptosis and has been implicated in tumorigenesis. Using a computational systems biology approach, followed by biochemical and functional validation, we have characterized the role of the STK38 kinase, an NDR family serine-threonine kinase, as a key modulator of MYC transcriptional activity in human B cells, affecting MYC protein stability in a signal-dependent fashion. Specifically, we show that in human B lymphoma ST486 cells STK38 is a key mediator of BCR pathway signaling, affecting MYC protein turnover and its phosphorylation at Ser62 in kinase-activity-dependent manner. STK38 inactivation abrogates apoptosis following BCR activation while its silencing mediates MYC protein degradation via canonical proteolytic pathways. This suggests that STK38 could provide an effective therapeutic target in MYC-dependent malignancies.
STK38 is a critical upstream regulator of MYC's oncogenic activity in human B-cell lymphoma.
Cell line, Time
View SamplesTissues of Arabidopsis plants overexpressing artificial microRNAs were compared to wild_type and respective target gene mutants (duplicate arrays)
Highly specific gene silencing by artificial microRNAs in Arabidopsis.
Specimen part
View SamplesThe pre-synaptic protein -synuclein is a key player in the pathogenesis of Parkinson's disease. Together with accumulation and missfolding of -synuclein protofibrils serve as seed structures for the aggregation of numerous proteins in the cytoplasm of neuronal cells, the so-called Lewy bodies. Furthermore, missense mutations in the SNCA gene and gene multiplications lead to autosomal dominant forms of familiar PD. However, so far the exact biological role of -synuclein in normal brain is elusive. To gain more insights into the biological function of this protein we monitored whole genome expression changes in dopaminergic neuroblastoma cells (SH-SY5Y) caused by a 90% reduction of -synuclein by RNA interference.
Microarray expression analysis of human dopaminergic neuroblastoma cells after RNA interference of SNCA--a key player in the pathogenesis of Parkinson's disease.
No sample metadata fields
View SamplesT2 progenies of two transgenic lines overexpressing ERF transcription factor WIN1 were grown on soil in parallel under identical conditions. mRNA was extracted from pooled leaves from multiple plants of each line for the microarray experiement.
WIN1, a transcriptional activator of epidermal wax accumulation in Arabidopsis.
No sample metadata fields
View SamplesSMART-seq2 was performed on single cells isolated from visually staged zebrafish embryos. Overall design: Samples were all sequenced in one batch. Some were generated with a 5'' UMI-tagged method, and others are full-length SMART-seq2.
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Cell line, Treatment, Time
View SamplesWild-type zebrafish embryos were mechanically dissociated and profiled using Drop-seq Overall design: Drop-seq was performed on 28 groups of 20-40 visually staged, mechanically dissociated embryos. Samples were combined and sequenced in batches DS2-DS5.
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Subject
View SamplesSubstantial effort is currently devoted to identifying cancer-associated alterations using genomics. Here, we show that standard blood collection procedures rapidly change the transcriptional and post-transcriptional landscapes of hematopoietic cells, resulting in biased activation of specific biological pathways, up-regulation of pseudogenes, antisense RNAs, and unannotated coding isoforms, and RNA surveillance inhibition. Affected genes include common mutational targets and thousands of other genes participating in processes such as chromatin modification, RNA splicing, T and B cell activation, and NF-?B signaling. The majority of published leukemic transcriptomes exhibit signals of this incubation-induced dysregulation, explaining up to 40% of differences in gene expression and alternative splicing between leukemias and reference normal transcriptomes. The effects of sample processing are particularly evident in pan-cancer analyses. We provide biomarkers that detect prolonged incubation of individual samples, and show that keeping blood on ice markedly reduces changes to the transcriptome. In addition to highlighting the potentially confounding effects of technical artifacts in cancer genomics data, our study emphasizes the need to survey the diversity of normal as well as neoplastic cells when characterizing tumors. This study is complemented by GSE61410: transcriptomic profiling of bone marrow cells from healthy individuals. Overall design: Peripheral blood mononuclear cells (PBMCs) were isolated from four healthy individuals, following an ex vivo incubation of variable length at either room temperature or on ice. RNA transcriptomes were measured using the Illumina HiSeq.
Sample processing obscures cancer-specific alterations in leukemic transcriptomes.
No sample metadata fields
View SamplesThe transcriptomic changes induced in the human liver cell line HepG2 by 7M of cisplatin after treatment for 12, 24 and 48h
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Cell line, Treatment, Time
View SamplesThe transcriptomic changes induced in primary mouse hepatocytes (C57BL/6 ) by 7M of cisplatin after treatment for 24 and 48h
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Cell line, Treatment, Time
View Samples