Downregulation of ubiquitin-associated protein 2-like with a short hairpin RNA inhibits human glioma cell growth in vitro

Zhao, Bing; Zong, Gang; Xie, Yongsheng; Li, Jia; Wang, Hongliang; Bian, Erbao

doi:10.3892/ijmm.2015.2323

Cited by 22 publications

(30 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It can interact with BIM1 to form a complex that modulates hematopoietic stem cell activity [24]. Numerous studies indicated its association with various types of cancer [25][26][27][28][29][30]. It is required for the accurate distribution of chromosomes during mitosis [31].…”

Section: Introductionmentioning

confidence: 99%

UBAP2L arginine methylation by PRMT1 modulates stress granule assembly

et al. 2019

View full text Add to dashboard Cite

Stress granules (SGs) are discrete assemblies of stalled messenger ribonucleoprotein complexes (mRNPs) that form when eukaryotic cells encounter environmental stress. RNA-binding proteins (RBPs) mediate their condensation by recruiting populations of mRNPs. However, the cellular and molecular mechanisms underlying the role of ubiquitin-associated protein 2-like (UBAP2L) in the regulation of SG dynamics remain elusive. Here, we show that UBAP2L is required for both SG assembly and disassembly. UBAP2L overexpression nucleated SGs under stress-null conditions. The UBAP2L Arg-Gly-Gly (RGG) motif was required for SG competence, and mediated the recruitment of SG components, including mRNPs, RBPs, and ribosomal subunits. The domain of unknown function (DUF) of UBAP2L-mediated interaction with ras GTPase-activating protein-binding protein (G3BP)1/2, and its deletion caused the cytoplasmic-nuclear transport of UBAP2L and G3BP1/2, thereby compromising SG formation. The protein arginine methyltransferase PRMT1 asymmetrically dimethylated UBAP2L by targeting the RGG motif. Increased arginine methylation blocked, whereas its decrease enhanced UBAP2L interactions with SG components, ablating and promoting SG assembly, respectively. These results provide new insights into the mechanisms by which UBAP2L regulates SG dynamics and RNA metabolism.

show abstract

Section: Introductionmentioning

confidence: 99%

UBAP2L arginine methylation by PRMT1 modulates stress granule assembly

et al. 2019

View full text Add to dashboard Cite

show abstract

“…However, as a component of BMI1-containing protein complexes, whether UBAP2L plays a role in EMT is unclear. Recent studies have demonstrated that UBAP2L expression is increased in myeloma and HCC [20-22] and involved in the growth and migration of glioma and prostate cancer [23, 24]; however, the function of UBAP2L in HCC has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of UBAP2L Inhibits the Epithelial-Mesenchymal Transition via SNAIL1 Regulation in Hepatocellular Carcinoma Cells

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Dysregulation of ubiquitin-associated protein 2-like (UBAP2L) has been reported in tumors, but its role in hepatocellular carcinoma (HCC) progression is unclear. Methods: The expression levels of UBAP2L in HCC tissues and HCC cell lines were detected by western blot and quantitative real-time (qRT) PCR. The effects of UBAP2L expression on HCC cell biological traits, including migration and invasion, were investigated by wound healing assay and matrigel transwell assay. Simultaneously, the expression of epithelial-mesenchymal transition (EMT) markers including E-cadherin, CK-18, N-cadherin, Vimentin, Claudin7 and the promoter activity of E-cadherin were detected by western blot and qRT-PCR. Subsequently, role of SNAIL1 in UBAP2L-mediated EMT and the mechanism underlying UBAP2L-mediated SNAIL1 expression were further investigated. Results: UBAP2L was overexpressed in human HCC tissues compared with peri-tumoral tissues. Downregulation of UBAP2L inhibited migration, invasion and the EMT in highly metastatic HCC cell lines. Furthermore, UBAP2L knockdown inhibited expression of the transcriptional repressor SNAIL1 and its ability to bind to the E-cadherin promoter via SMAD2 signaling pathway, which in turn resulted in increased E-cadherin expression. Additionally, bioinformatics analysis showed that expression of UBAP2L is correlated with poor prognosis in patients with HCC. Conclusions: UBAP2L plays a critical role in maintenance of the metastatic ability of HCC cells via SNAIL1 Regulation and is predictive of a poor clinical outcome.

show abstract

“…Aside from neurodegeneration, a number of publications show a role of UBAP2L in cancer. UBAP2L appears to act in different malignances as an oncogene, whose expression is required for survival (Chai et al, 2016), growth (He et al, 2018; Li and Huang, 2014; Li et al, 2018; Zhao et al, 2015), and metastasization (Aucagne et al, 2017; Li and Huang, 2014; Li et al, 2018; Ye et al, 2017). Stress granules are often present in cancer cells (reviewed in Mahboubi and Stochaj, 2017), where they may promote cell survival in the stressful condition of the cancer microenvironment (Adjibade et al, 2015; Somasekharan et al, 2015; Vilas-Boas et al, 2016) and metastasization (Somasekharan et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The relative stability of stress granule cores has recently allowed their purification and the identification of novel stress granule nucleators, among them the protein UBAP2L (Ubiquitin-associated protein 2-like (Markmiller et al, 2018; Youn et al, 2018). UBAP2L is a ubiquitous and abundant protein in human tissues (Beck et al, 2011; Lonsdale et al, 2013; Melé et al, 2015; Uhlén et al, 2015), it promotes cancer progression and metastasis (Aucagne et al, 2017; Chai et al, 2016; He et al, 2018; Li and Huang, 2014; Li et al, 2018; Ye et al, 2017, P. 20; Zhao et al, 2015) and may be involved in neurodegenerative diseases (Markmiller et al, 2018). Despite its abundance and potential implication in diseases, the exact role of UBAP2L in cell physiology and stress granule formation is not yet understood.…”

Section: Introductionmentioning

confidence: 99%

Molecularly distinct cores coexist inside stress granules

Cirillo

Cieren

Gotta

2019

Preprint

View full text Add to dashboard Cite

L.C.), 15 monica.gotta@unige.ch (M.G.) 16 17 18 RESULTS 76UBAP2L localizes inside stress granules in discrete particles distinct from G3BP1 77 cores. 78 Given the importance of UBAP2L in sodium arsenite (arsenite hereafter)-induced stress 79 granule assembly (Markmiller et al., 2018; Youn et al., 2018), we sought to investigate its 80 sublocalization inside stress granules. To this end, we used 3D-STED (3D Stimulated 81 Emission Depletion miscroscopy, Hell and Wichmann, 1994; Klar and Hell, 1999). 3D-STED 82 immunofluorescence of HeLa K cells fixed and stained with anti-UBAP2L antibodies, 83 revealed that each stress granule is formed by discrete UBAP2L particles of roughly round 84 shape ( Fig. 1 A), with a diameter of 187.0 ± 44.2 nm (mean ± SD, Fig. 1 B). We also 85 performed 3D-STED on HeLa K cells stained for the known stress granule component 86 G3BP1 and measured the diameter of G3BP1 cores ( Fig. 1 A). Our analysis revealed a 87 diameter of 182.7 ± 41.9 nm (mean ± SD), which is in good agreement with the published 88 diameter of 190.8 ± 28.3 nm (Fig. 1B, Jain et al., 2016). The number of UBAP2L and G3BP1 89 particles linearly correlated with the stress granule volume ( Fig. S1 A). The localization of 90 UBAP2L in discrete particles and their size distribution suggest that UBAP2L localizes to 91 stress granule cores. 92The shell and the core of stress granules do not only differ in their composition, but also in 93 the dynamics of their components, with core proteins being more stable and shell proteins 94 more dynamic. To assess whether UBAP2L particles are stress granule cores, we measured 95 the dynamics of UBAP2L in living cells. To visualize UBAP2L, we tagged endogenous 96 UBAP2L at the C-terminus with the red fluorescent protein mScarlet using CRISPR-Cas9 97 (Fig. S1 B Bindels et al., 2017). Clones were screened via PCR (Polymerase Chain 98 Reaction, Fig. S1 C) and validated with western blot using an anti-UBAP2L antibody (Fig. 99 S1 D). In addition, treatment of UBAP2L-mScarlet HeLa cells with a siRNA directed against 100 mScarlet, followed by western blot analysis, confirmed the successful insertion of the 101 construct (Fig. S1 E). Although we failed to identify a homozygous insertion (Fig. S1 D, E), 102 live cell imaging revealed that UBAP2L-mScarlet transitions from a diffuse cytosolic signal 103 to a droplet-like pattern following arsenite exposure (Fig. S1 F). This observation is 104 consistent with published immunofluorescence of UBAP2L (Markmiller et al., 2018; Youn et 105 al., 2018), indicating that UBAP2L-mScarlet recapitulates the localization of wild-type 106 UBAP2L. Having created a tool to visualize UBAP2L in vivo, we next measured the 107 dynamics of UBAP2L in stress granules using Fluorescence Recovery after Photobleaching 108 (FRAP). After treating UBAP2L-mScarlet HeLa cells with arsenite to induce stress granule 109 6 formation, we bleached a single cytosolic granule and followed the fluorescence recovery 110 over time using confocal microscopy (Fig. 1 C). Analysis of fluo...

show abstract

Downregulation of ubiquitin-associated protein 2-like with a short hairpin RNA inhibits human glioma cell growth in vitro

Cited by 22 publications

References 26 publications

UBAP2L arginine methylation by PRMT1 modulates stress granule assembly

UBAP2L arginine methylation by PRMT1 modulates stress granule assembly

Downregulation of UBAP2L Inhibits the Epithelial-Mesenchymal Transition via SNAIL1 Regulation in Hepatocellular Carcinoma Cells

Molecularly distinct cores coexist inside stress granules

Contact Info

Product

Resources

About