Purpose: We identified KPC1 as the ubiquitin ligase that binds to the p105 precursor of NF-kB, ubiquitinates it and mediates its proteasomal processing to generate the p50 active subunit of the transcription factor. Using U87-MG human glioblastoma xenografts, we observed that overexpression of KPC1 results in strong inhibition of tumor growth mediated via excessive generation of p50.The goal of this RNASeq study was to analyze the profile of gene expression in xenografts overexpressing control (V0), KPC1 or p50 vectors, and to further understand how the altered gene expression patterns can explain the tumor suppressive effect we observed. Results:Transcript analysis of U87-MG xenografts overexpressing control (V0), KPC1 or p50 vector mapped to the human genome revealed: • A strong similarity between overexpression of p50 and KPC1 (correlation of 0.51, p-value<10-300 ) • A specific signature of NF-kB targets [21 of the consistently changed genes are known to be regulated by NF-kB (p-value<3.4×10-9 )] • A significant (p-value<1.4×10-18) increase in the expression of 40 tumor suppressor genes, with no significant change in other classes. • A significant down regulation of a cluster of genes including LIN28B, IL-6, HMAGA2 and VEGFA. This finding links well to an established regulatory axis involving LIN28B, Let-7 microRNA, and IL-6 in inflammation and cell transformation that is regulated by NF-kB. Overall design: Exponentially growing U87-MG cells were stably transfected with an empty vector (V0) or vectors coding for Myc-KPC1 or Flag-p50. Cells were dissociated with trypsin, washed with PBS, and brought to a concentration of 50×10^6 cells/ml. Cell suspension (5×10^6/0.1 ml) was inoculated subcutaneously at the right flank of 7-weeks old male Balb/C nude mice (n=7). Following 21 days, mRNA from U87-MG xenografts was isolated using an RNA purification kit, and analyzed using the Illumina HiSeq 2500 sequencer. The RNASeq analysis experiment was repeated twice independently. Run1 included a total of 7 samples. Samples 1-3 were isolated from V0 – control tumors (3 different tumors), samples 4-5 were isolated from KPC1-expressing tumors (2 different pools of 3 tumors each due to small tumor size), and samples 6-7 were isolated from p50-expressing tumors for (2 different pools of 2-3 tumors each, due to very small tumor size). Run2 included a total of 5 samples. Samples 8-10 were isolated from V0 (control) tumors (3 different tumors), samples 11-12 were isolated from KPC1 tumors (2 different pools of 3 tumors each due to small tumor size). Several repeated attempts to extract RNA from the p50-expressing tumors did not yield any results, as the tumors were miniscule.
KPC1-mediated ubiquitination and proteasomal processing of NF-κB1 p105 to p50 restricts tumor growth.
No sample metadata fields
View SamplesUsing microarray analysis, we explored the differences in gene expression in wounded and intact skin using murine model. Injured skin samples were examined at days 1 and 4 post injury.
Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate.
Specimen part, Time
View SamplesIn depth temporal profiling of transcript changes at 10 time points during germination in Arabidopsis seed was carried out. The time course utilised, encompassed seed maturation, stratification, germination and post-germination and provided a global investigation into the tightly regulated, phasic changes that define seed germination.
In-depth temporal transcriptome profiling reveals a crucial developmental switch with roles for RNA processing and organelle metabolism that are essential for germination in Arabidopsis.
Specimen part, Disease, Time
View SamplesIn response to bacterial infection, early transcriptional re-programming occurs in the host plant.
Antagonistic, overlapping and distinct responses to biotic stress in rice (Oryza sativa) and interactions with abiotic stress.
Specimen part
View SamplesIn response to WRKY40 and WRKY60 perturbation (and high light stress), significant transcriptional re-programming occurs particularly for genes encoding stress responsive mitochondrial and choloplast proteins.
AtWRKY40 and AtWRKY63 modulate the expression of stress-responsive nuclear genes encoding mitochondrial and chloroplast proteins.
Specimen part, Treatment
View SamplesTranscript abundance profiles were examined over the first 24 hours of germination in rice grown under aerobic conditions.
Experimental analysis of the rice mitochondrial proteome, its biogenesis, and heterogeneity.
Specimen part, Time
View SamplesThe antagonistic interaction between iron (Fe) and phosphorus (P) has been noted in the area of plant nutrition. To understand the physiology and molecular mechanisms of this interaction, we studied the growth performance, nutrient concentration, and gene expression profiles of root and shoot segments derived from 10-d-old rice (Oryza sativa) seedlings under four different nutrient conditions: (1) full strength of Fe and P (+Fe+P); (2) full strength of P and no Fe (-Fe+P); (3) full strength of Fe and no P (+Fe-P); and (4) without both Fe and P (-Fe-P).
Physiological and transcriptome analysis of iron and phosphorus interaction in rice seedlings.
Specimen part
View SamplesAnalysis of changes in global transcript abundance profiles of 2 week old tim23 OE (overexpressor) and tim23 KO (knock-out) mutant Arabidopsis plants complared to wild-type (Col-0) using Affymetrix GeneChipル Arabidopsis ATH1 Genome Arrays.
Dual location of the mitochondrial preprotein transporters B14.7 and Tim23-2 in complex I and the TIM17:23 complex in Arabidopsis links mitochondrial activity and biogenesis.
Age, Specimen part
View SamplesArabidopsis ABA hpersensitive germination2-1 mutant shows an enhanced sensitivity to ABA. This mutant has higher levels of endogenous ABA. This mutant also exhibited SA hypersensitivity and dwarf phenotype. Regarding SA hypersensitivity, ahg2-1 exhibits higher endogenous SA level and an enhanced resistance to pathogenic bacteria. Since AHG2 encodes the Arabidopsis polyA specific ribonuclease that is involved in mRNA degradation, presumably abnormal accumulation of some mRNAs confers the unique phenotype. Transcriptome analyses are expected to offer information on the target of AHG2. In order to eliminate secondary effects of higher levels of ABA and SA, ahg2-1abi1-1 and ahg2-1sid2-2 double mutants were also examined. The transcriptome data revealed that; ahg2-1 confers unique gene expression profiles, ABA and SA affect the expression profiles of this mutant but many genes are independent of those plant hormone responses. Comparing with expression profiles of other mutants indicated that the ahg2-1 might affect mitochondrial function.
ABA hypersensitive germination2-1 causes the activation of both abscisic acid and salicylic acid responses in Arabidopsis.
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View SamplesMale germ cells express the widest repertoire of transcript variants in mammalian tissues. Nevertheless, factors and mechanisms underlying such pronounced diversity are largely unknown. The splicing regulator Sam68 is highly expressed in meiotic cells and its ablation results in defective spermatogenesis. Herein, we uncover an extensive splicing program operated by Sam68 across meiosis, primarily characterized by alternative last exon (ALE) regulation in genes of functional relevance for spermatogenesis. Lack of Sam68 preferentially causes premature transcript termination at internal polyadenylation sites. Overall design: RNA-Seq data for purified spermatocytes and spermatids isolated from Sam68+/+ and Sam68-/- mice.
Functional Interaction between U1snRNP and Sam68 Insures Proper 3' End Pre-mRNA Processing during Germ Cell Differentiation.
Specimen part, Cell line, Subject
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