UHMK1 is a splicing regulatory kinase
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE199768 | GEO | 2023/03/24
REPOSITORIES: GEO
Similar Datasets
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:UHMK1 is a splicing regulatory kinase
| PRJNA821472 | ENA
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.
2019-06-18 | GSE121733 | GEO
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.
2012-09-05 | GSE38097 | GEO
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:Characterization of RNA processing events dependent on U2AF-related proteins PUF60 and RBM39. PUF60 (poly-U-binding factor 60 kDa, also known as FIR, Hfp or Ro-bp1) is a splicing factor homologous to the 65 kD subunit of the auxiliary factor of U2 small nuclear ribonucleoprotein (U2AF65). PUF60 has two central RNA recognition motifs and a C-terminal U2AF homology motif (UHM), but lacks the N terminal arginine/serine-rich (RS) and UHM ligand motif (ULM) domains present in U2AF65. PUF60 activity, in conjunction with U2AF, facilitates the association of U2 snRNP with the pre-mRNA. PUF60 and U2AF65 can bind SF3b155 ULMs simultaneously and noncompetitively. RBM39 (also known as CAPERα, HCC1, FSAP59 or RNPC2) is an RNA processing factor and a hormone-dependent transcriptional coactivator. RBM39 domain structure is similar to PUF60, except for the extra N-terminal RS domain with unknown function. To understand function of the two proteins on a genome-wide scale, each protein was individually depleted from human embryonic kidney cell line 293 using RNAi to systematically characterize the PUF60- and RBM39-dependent exon usage.
2018-05-25 | E-MTAB-6010 | 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:To explore the mechanism by which UHMK1 enhances the transcriptional activation of ATF4, we used tandem mass spectrometry (MS/MS) to analyze the UHMK1 immunocomplex isolated from HEK293T cells.
2020-01-24 | PXD015693 | Pride
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
Project description:A key step in pre-mRNA splicing is the recognition of 3’ splicing sites by the U2AF large and small subunits, a process regulated by numerous trans-acting splicing factors. How these trans-acting factors interact with U2AF in vivo is unclear. From a screen for suppressors of the temperature-sensitive (ts) lethality of the C. elegans U2AF large subunit gene uaf-1(n4588) mutants, we identified mutations in the RNA binding motif gene rbm-5, a homolog of the tumor suppressor RBM5. rbm-5 mutations can suppress uaf-1(n4588) ts-lethality by loss of function and neuronal expression of rbm-5 was sufficient to rescue the suppression. Transcriptome analyses indicate that uaf-1(n4588) affected the expression of numerous genes and rbm-5 mutations can partially reverse the abnormal gene expression to levels similar to that of wild type. Though rbm-5 mutations did not obviously affect alternative splicing per se, they can suppress or enhance, in a gene-specific manner, the altered splicing of genes in uaf-1(n4588) mutants. Specifically, the recognition of a weak 3’ splice site was more susceptible to the effect of rbm-5. Our findings provide novel in vivo evidence that RBM-5 can modulate UAF-1-dependent RNA splicing and suggest that RBM5 might interact with U2AF large subunit to affect tumor formation.
2018-06-13 | GSE115695 | GEO