Phosphorylation of Cajal body protein coilin activated by UHMK1 influences the sensitivity of colon cancer cells to 5-FU
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ABSTRACT:
PROVIDER: PRJNA714432 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13961690_1.fastq.gz | Fastqsanger.gz | |||
| SRR13961690_2.fastq.gz | Fastqsanger.gz | |||
| SRR13961691_1.fastq.gz | Fastqsanger.gz | |||
| SRR13961691_2.fastq.gz | Fastqsanger.gz | |||
| SRR13961692_1.fastq.gz | Fastqsanger.gz |
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Project description:Drug resistance to 5-fluorouracil (5-FU) and recurrence after chemotherapy in colorectal cancer remain a challenge to be resolved for the improvement of patient outcomes. In the present study, we found that the application of conditioned medium (CM) derived from 5-FU-resistant colon cancer cells HCT-8/FU reduced the chemosensitivity of native HCT-8 to 5-FU, which was accompanied with the significant changes at number counts and morphology of Cajal bodys (CBs), a spherical nuclear body, dynamic exchanging constituent macromolecules (i.e., body-specific proteins and RNAs) with the nucleoplasmic space.It was shown that the disassembly and reassembly of CBs regulated by the phosphorylation of coilin, which was significantly activated by UHMK1. These led to a large number of variations of RNA alternative splicing in cells, which could contribute to the cell survival through remodeling of intracellular phenotype and transmitting preadaptive signal to adjacent cells in tumor microenvironment.
2021-03-15 | GSE168888 | GEO
Project description:The cell nucleus contains distinct biomolecular condensates that form at specific genetic loci, organize chromosomes in 3D space, and regulate RNA processing. Among these, Cajal bodies (CBs) require key “scaffolding” proteins for their assembly, which is not fully understood. Here we employ proximity biotinylation, mass spectrometry, and functional screening to comprehensively identify and test functions of CB components. We document 144 protein interactors of coilin, of which 70 were newly detected, and establish 25 players needed for CB assembly and/or maintenance. Surprisingly, depletion of nine coilin interactors – mostly constituents of the 60S ribosome (RPLs) – increased CB number and caused subdomains defined by coilin and the Survival of Motor Neuron protein (SMN) to merge. These phenotypes were traceable to altered nuclear levels of dimethylarginine. Our data implicate RPL24 and other players in the regulation of CBs by modulating post-translational modifications. Moreover, the prevalence of transcription factors among the identified components highlights roles for gene activity in CB assembly and nuclear positioning.
2024-11-10 | PXD042406 | Pride
Project description:Cajal bodies (CBs) are membraneless organelles whose mechanism of formation is still not fully understood. Many proteins contribute to the formation of CBs, including Nopp140, WRAP53, and coilin. SUMOylation, a post-translational modification, of coilin involves multiple different lysine residues. Additionally, coilin is also found in the nucleoplasm where its role is still being understood. Here, we demonstrate a novel mechanism examining the interaction changes of coilin when its SUMOylation is disrupted. We look at both global SUMOylation inhibition and its effect on CB formation, as well as targeted SUMOylation inhibition of coilin itself in cells by developing a coilin SUMO mutant. We found upon two types of global SUMOylation inhibition, as well as upon transfection of the coilin SUMO mutant, that CBs increased in number and decreased in size. Additionally, we saw via coimmunoprecipitation the coilin SUMO mutant has altered interaction with Nopp140. This demonstrates increased mechanistic ties to CB formation and SUMOylation. Furthermore, RNA sequencing and small RNA sequencing on a primary cell line with few CBs showed that coilin impacts the response to lipopolysaccharide-induced stress. Collectively, our results identify SUMOylation as a novel mechanism driving CB formation and highlights a positive role for human coilin in innate immunity.
2025-04-30 | GSE268257 | GEO
Project description:Cajal bodies (CBs) are membraneless organelles whose mechanism of formation is still not fully understood. Many proteins contribute to the formation of CBs, including Nopp140, WRAP53, and coilin. SUMOylation, a post-translational modification, of coilin involves multiple different lysine residues. Additionally, coilin is also found in the nucleoplasm where its role is still being understood. Here, we demonstrate a novel mechanism examining the interaction changes of coilin when its SUMOylation is disrupted. We look at both global SUMOylation inhibition and its effect on CB formation, as well as targeted SUMOylation inhibition of coilin itself in cells by developing a coilin SUMO mutant. We found upon two types of global SUMOylation inhibition, as well as upon transfection of the coilin SUMO mutant, that CBs increased in number and decreased in size. Additionally, we saw via coimmunoprecipitation the coilin SUMO mutant has altered interaction with Nopp140. This demonstrates increased mechanistic ties to CB formation and SUMOylation. Furthermore, RNA sequencing and small RNA sequencing on a primary cell line with few CBs showed that coilin impacts the response to lipopolysaccharide-induced stress. Collectively, our results identify SUMOylation as a novel mechanism driving CB formation and highlights a positive role for human coilin in innate immunity.
2025-04-30 | GSE271895 | GEO
Project description:To investigate location of Cajal bodies (CB) inside the cell nucleus, we created a stable cell line expressing the GFP version of CB-marker protein coilin at endogenous levels and performed ChIP-seq with anti-EGFP antibody. ChIP-seq revealed close association of CBs wih U3 genes, snRNA genes and histone genes in histone cluster 1 and 2. 1 biological replicate of coilin ChIP-seq and input sample
2014-11-06 | E-GEOD-58449 | biostudies-arrayexpress
Project description:Coilin is a nuclear protein known for its roles in assembling the Cajal Body and participating in the biogenesis of ribonucleoproteins. We have uncovered novel functions for coilin in promoting microRNA biogenesis and the phosphorylation/SUMOylation of various proteins, through which we have observed a role for coilin in responding to stress signals. Coilin has also been found to participate in the stress response in plants through the regulated expression of immunity genes and activation of defense mechanisms. In this study, we further investigated this role of coilin in regulating the immune response by applying transcriptomic analyses to examine the response to lipopolysaccharide-mediated stress in coilin-depleted human cells and coilin mutant zebrafish embryos. Our results indicate a vital function for coilin in regulating the expression of immunity-related genes and establish a conserved role for vertebrate coilin in the promotion of the innate immune response across humans and zebrafish.
2025-04-30 | GSE273717 | GEO
Project description:To investigate location of Cajal bodies (CB) inside the cell nucleus, we created a stable cell line expressing the GFP version of CB-marker protein coilin at endogenous levels and performed ChIP-seq with anti-EGFP antibody. ChIP-seq revealed close association of CBs wih U3 genes, snRNA genes and histone genes in histone cluster 1 and 2.
2014-11-06 | GSE58449 | GEO
Project description:Resistance to 5-fluorouracil (5-FU) in chemotherapy and recurrence of colorectal tumors is a serious concern that impedes improvements to clinical outcomes. In the present study, we found that conditioned medium (CM) derived from 5-FU-resistant HCT-8/FU cells reduced 5-FU chemosensitivity in HCT-8 colon cancer cells, with corresponding changes to number and morphology of Cajal bodies (CBs) as observable nuclear structures. We found that U2AF homology motif kinase 1 (UHMK1) altered CB disassembly and reassembly and regulated the phosphorylation of coilin, a major component of CBs. This subsequently resulted in a large number of variations in RNA alternative splicing that affected cell survival following 5-FU treatment, induced changes in intracellular phenotype, and transmitted preadaptive signals to adjacent cells in the tumor microenvironment (TME). Our findings suggest that CBs may be useful for indicating drug sensitivity or resistance in tumor cells in response to stress signals. The results also suggest that UHMK1 may be an important factor for maintaining CB structure and morphology by regulating splicing events, especially following cellular exposure to cytotoxic drugs. Video Abstract.
| S-EPMC8841122 | biostudies-literature
Project description:Cajal bodies (CBs) are membraneless organelles whose mechanism of formation is still not fully understood. Many proteins contribute to the formation of CBs, including Nopp140 (NOLC1), WRAP53 and coilin. Coilin is modified on multiple different lysine residues by SUMO, the small ubiquitin-like modifier. In addition to its accumulation in CBs, coilin is also found in the nucleoplasm, where its role is still being evaluated. Here, we demonstrate a novel mechanism of CB regulation by examining the interaction changes of coilin when its SUMOylation is disrupted. The impact of global SUMOylation inhibition and targeted disruption of coilin SUMOylation on CB formation was examined. We found that two types of global SUMOylation inhibition and expression of SUMO-deficient coilin mutants increased CB number but decreased CB size. Additionally, we saw via coimmunoprecipitation that a SUMO-deficient coilin mutant has altered interaction with Nopp140. This demonstrates increased mechanistic ties between CB formation and SUMOylation.
| S-EPMC11827600 | biostudies-literature
Project description:p53 influences 5-FU-induced chromatin accessibility [ATAC-seq]
| PRJNA663471 | ENA