The protein kinase KIS impacts gene expression in the neonate brain
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE38097 | GEO | 2012/09/05
SECONDARY ACCESSION(S): PRJNA167203
REPOSITORIES: GEO
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Project description:The protein kinase KIS (product of the gene UHMK1) is expressed during mouse brain development and is proposed to control gene expression through the phosphorylation of splicing factor SF1. We compared the expression of transcripts in wild type and KIS-ko newborn mouse brain (females) using affymetrix exon 1st arrays. Six pairs of wildtype and KIS-ko brains from littermate female newborn mice were processed for Affymetrix exon 1st array hybridization. Analysis was performed at the exon level using PLIER normalisation and the Affymetrix Expression Console.
2012-09-05 | E-GEOD-38097 | biostudies-arrayexpress
Project description:The U2AF Homology Motif Kinase 1 (UHMK1) is the only kinase that contains the U2AF homology motif (UHM), a common protein interaction domain among splicing factors. Through this motif, UHMK1 interacts with the splicing factors SF1 and SF3B1, known to participate in early steps of spliceosome assembly and 3’ splice site recognition. Also, UHMK1 phosphorylates these splicing factors in vitro. Despite that, the involvement of UHMK1 in RNA processing has never been demonstrated. Here, we submitted UHMK1-overexpressing or -depleted NIH3T3 cells RNAseq analysis to evaluate UHMK1 contribution to gene expression and splicing.
2023-03-24 | GSE199768 | GEO
Project description:The U2AF Homology Motif Kinase 1 (UHMK1) is the only kinase that contains the U2AF homology motif (UHM), a common protein interaction domain among splicing factors. Through this motif, UHMK1 interacts with the splicing factors SF1 and SF3B1, known to participate in the 3’ splice site recognition and early steps of spliceosome assembly. Also, UHMK1 phosphorylates these splicing factors in vitro. However, the involvement of UHMK1 in RNA processing has not previously been demonstrated. Here, we used global phosphoproteomics to identify novel putative substrates in UHMK1-overexpressing or -depleted (knockdown) NIH3T3 cells and better characterize the function of this kinase in splicing and other biological processes.
2023-05-02 | PXD033353 | Pride
Project description:Kinase inhibitors (KIs) represent an important class of anti-cancer drugs. Although cardiotoxicity is a serious adverse event associated with several KIs, the reasons remain poorly understood and its prediction remains challenging. Here, we perform transcriptomic profiling of human heart-derived primary cardiomyocyte cell lines treated with a panel of 26 FDA-approved KIs and classify their effects on subcellular pathways and processes. Individual cardiotoxicity patient reports for these KIs, obtained from the FDA Adverse Event Reporting System, are used to compute relative risk scores. These are then combined with cell line-derived transcriptomic datasets through elastic net regression analysis to identify a gene signature that can predict risk of cardiotoxicity. We also identify relationships between cardiotoxicity risk and structural/binding profiles of individual KIs. We conclude that acute transcriptomic changes in cell-based assays combined with drug substructures are predictive of KI-induced cardiotoxicity risk, and that they can be informative for future drug discovery.
2020-05-13 | GSE146096 | GEO
Project description:Kinase inhibitors (KIs) represent an important class of anti-cancer drugs. Although cardiotoxicity is a serious adverse event associated with several KIs, the reasons remain poorly understood and its prediction remains challenging. Here, we perform transcriptomic profiling of human heart-derived primary cardiomyocyte cell lines treated with a panel of 26 FDA-approved KIs and classify their effects on subcellular pathways and processes. Individual cardiotoxicity patient reports for these KIs, obtained from the FDA Adverse Event Reporting System, are used to compute relative risk scores. These are then combined with cell line-derived transcriptomic datasets through elastic net regression analysis to identify a gene signature that can predict risk of cardiotoxicity. We also identify relationships between cardiotoxicity risk and structural/binding profiles of individual KIs. We conclude that acute transcriptomic changes in cell-based assays combined with drug substructures are predictive of KI-induced cardiotoxicity risk, and that they can be informative for future drug discovery.
2020-05-13 | GSE146095 | GEO
Project description:The impact of the kinase UHMK1 on liver cancer cells is unknown. In order to identify UHMK1-dependent genes, UHMK1 was inhibited by siRNA in comparison to nonsense-siRNA-transfected cells.
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Project description:We sequenced total 10 virus infected mouse hippocampus: 3 samples of lentivirus infected, 4 samples of 1st batch retrovirus infected as batch A, and 3 samples as batch B retrovirus infected. Examination of mRNA levels using TU-tagging approach that differ the newborn neurons from mature neurons.
2016-10-25 | E-GEOD-76587 | biostudies-arrayexpress
Project description:Neurons and endocrine cells package peptides in secretory granules (large dense core vesicles; LDCVs) for storage and stimulated release. Studies of PAM, an essential secretory granule membrane enzyme, revealed a pathway that can relay information from secretory granules to the nucleus, resulting in alterations in gene expression. The cytosolic domain of PAM, a type 1 membrane enzyme essential for the production of amidated peptides, is basally phosphorylated by Uhmk1 and other Ser/Thr kinases. Proopiomelanocortin processing in AtT-20 corticotrope tumor cells was increased when Uhmk1 expression was reduced. Uhmk1 was concentrated in the nucleus, but cycled rapidly between nucleus and cytosol. Endoproteolytic cleavage of PAM releases a soluble cytosolic domain (CD) fragment that localizes to the nucleus. Localization of PAM-CD to the nucleus was decreased when PAM-CD with phosphomimetic mutations was examined and when active Uhmk1 was simultaneously over-expressed. Membrane-tethering Uhmk1 did not eliminate its ability to exclude PAM-CD from the nucleus, suggesting that cytosolic Uhmk1 could cause this response. Microarray analysis demonstrated the ability of PAM to increase expression of a small subset of genes, including aquaporin 1 (Aqp1) in AtT-20 cells. Aqp1 mRNA levels were higher in wildtype mice than in mice heterozygous for PAM, indicating that a similar relationship occurs in vivo. Expression of PAM-CD also increased Aqp1 levels while expression of Uhmk1 diminished Aqp1 expression. The outlines of a pathway that ties secretory granule metabolism to the transcriptome are thus apparent. Three separate clones of AtT-20 mouse corticotrope tumor cells stably transfected with doxycycline-inducible rat PAM-1 (clones 14, 6_1, 6_2) were treated with cotrol or doxycycline medium for 48 hours. Total mRNA was isolated and hybridized to an Illumina MouseWG-6 v 2.0 whole genome BeadChip.
2010-07-29 | E-GEOD-22509 | biostudies-arrayexpress
Project description:We report RNAseq analysis of KIS-1 cells with and without doxycycline-inducible expression of the EBF1 transcription factor. We also compared untreated KIS-1 WT cells to RAJI WT cells.
2021-01-21 | GSE136920 | GEO
Project description:Neurons and endocrine cells package peptides in secretory granules (large dense core vesicles; LDCVs) for storage and stimulated release. Studies of PAM, an essential secretory granule membrane enzyme, revealed a pathway that can relay information from secretory granules to the nucleus, resulting in alterations in gene expression. The cytosolic domain of PAM, a type 1 membrane enzyme essential for the production of amidated peptides, is basally phosphorylated by Uhmk1 and other Ser/Thr kinases. Proopiomelanocortin processing in AtT-20 corticotrope tumor cells was increased when Uhmk1 expression was reduced. Uhmk1 was concentrated in the nucleus, but cycled rapidly between nucleus and cytosol. Endoproteolytic cleavage of PAM releases a soluble cytosolic domain (CD) fragment that localizes to the nucleus. Localization of PAM-CD to the nucleus was decreased when PAM-CD with phosphomimetic mutations was examined and when active Uhmk1 was simultaneously over-expressed. Membrane-tethering Uhmk1 did not eliminate its ability to exclude PAM-CD from the nucleus, suggesting that cytosolic Uhmk1 could cause this response. Microarray analysis demonstrated the ability of PAM to increase expression of a small subset of genes, including aquaporin 1 (Aqp1) in AtT-20 cells. Aqp1 mRNA levels were higher in wildtype mice than in mice heterozygous for PAM, indicating that a similar relationship occurs in vivo. Expression of PAM-CD also increased Aqp1 levels while expression of Uhmk1 diminished Aqp1 expression. The outlines of a pathway that ties secretory granule metabolism to the transcriptome are thus apparent.
2010-06-23 | GSE22509 | GEO