We identified two isoforms of human MKL1 that differ in their N-terminal domains. Since MKL1 is a transcriptional coactivator of SRF and regulates many SRF target genes, we wanted to analyze if transcription is differentially regulated by the two isoforms upon stimulation of the Rho-actin-MKL1-SRF pathway.
TGF-β-induced differentiation into myofibroblasts involves specific regulation of two MKL1 isoforms.
Cell line
View SamplesTransfer RNA (tRNA) modifications enhance the efficiency, specificity and fidelity of translation in all organisms. The anticodon modification mcm5s2U34 is required for normal growth and stress resistance in yeast; mutants lacking this modification have numerous phenotypes. Mutations in the homologous human genes are linked to neurological disease. The yeast phenotypes can be ameliorated by overexpression of specific tRNAs, suggesting that the modifications are necessary for efficient translation of specific codons. We determined the in vivo ribosome distributions at single codon resolution in yeast strains lacking mcm5s2U. We found accumulations at AAA, CAA, and GAA codons, suggesting that translation is slow when these codons are in the ribosomal A site, but these changes appeared too small to affect protein output. Instead, we observed activation of the GCN4-mediated stress response by a non- canonical pathway. Thus, loss of mcm5s2U causes global effects on gene expression due to perturbation of cellular signaling. Overall design: WT yeast and mutants lacking anticodon tRNA modifications were grown in YPD, and subjected to ribosome footprint profiling (ribo-seq) and RNA-seq of poly-A selected RNA. Dataset contains biological replicates for WT, ?ncs6 and ?uba4. Technical replicates were also performed for all RNA-seq datasets (using a different poly-A selection method).
Loss of a conserved tRNA anticodon modification perturbs cellular signaling.
Cell line, Subject
View SamplesSOX9 is generally not expressed in melanomas with a high proliferative capacity but is expressed in melanomas with a high invasive capacity. Here we overexpress full length SOX9 in M010817, a melanoma cell culture with high proliferative capacity but low invasive capacity.
Methylation-dependent SOX9 expression mediates invasion in human melanoma cells and is a negative prognostic factor in advanced melanoma.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans.
Sex, Age, Specimen part, Disease, Race, Subject
View SamplesTranslational Relevance
Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans.
Sex, Age, Race, Subject
View SamplesRON WT and RON KO at 5, 6, 7 week virgin mammary glands
The Ron receptor tyrosine kinase negatively regulates mammary gland branching morphogenesis.
Age
View SamplesWe have shown that Sox10 plays a crucial role in the initiation and maintenance of giant congenital nevi and melanoma in a mouse model of melanoma.To dissect the molecular mechanisms and analyze the role of SOX10 in the maintenance of human melanoma, we have performed microarray study.
Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma.
Cell line, Treatment, Time
View SamplesMutations involving the NFKB pathway are present in at least 17% of multiple myeloma (MM) tumors and 40% of MM cell lines (MMCL). These mutations, which are thought to be progression events, enable MM tumors to become less dependent on extrinsic bone marrow signals that activate NFKB. Studies on a panel of 50 MMCL provide some clarification of the mechanisms through which these mutations act and the significance of classical vs alternative activation of NFKB. First, only one mutation (NFKB2) selectively activates the alternative pathway, whereas several mutations (CYLD, NFKB1, TACI) selectively activate the classical pathway. However, most mutations affecting NIK level (NIK, TRAF2, TRAF3, cIAP1&2, CD40) activate the alternative but often both pathways. Second, we confirm the critical role of TRAF2 in regulating NIK degradation, whereas TRAF3 enhances but is not essential for cIAP1/2-mediated proteosomal degradation of NIK in MM.
Classical and/or alternative NF-kappaB pathway activation in multiple myeloma.
Cell line
View SamplesIncreased activity of the epigenetic modifier EZH2 has been associated with different cancers. However, evidence for a functional role of EZH2 in tumourigenesis in vivo remains poor, in particular in metastasising solid cancers. Here we reveal central roles of EZH2 in promoting growth and metastasis of cutaneous melanoma. In a melanoma mouse model, conditional Ezh2 ablation as much as treatment with the preclinical Ezh2 inhibitor GSK503 stabilises the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology. Comparably, in human melanoma cells, EZH2 inactivation impairs proliferation and invasiveness, accompanied by re-expression of tumour suppressors connected to increased patient survival. These EZH2 target genes suppress melanoma growth and prevent EMT / metastasis in vivo revealing the dual function of EZH2 in promoting tumour progression. Thus, EZH2-mediated epigenetic repression is highly relevant especially during advanced melanomagenesis, which makes EZH2 a promising target for novel melanoma therapies.
The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The thrombopoietin/MPL axis is activated in the Gata1<sup>low</sup> mouse model of myelofibrosis and is associated with a defective RPS14 signature.
Sex
View Samples