Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway

Quaresma, Alexandre J.C.; Sievert, Rachel A.; Nickerson, Jeffrey A.

doi:10.1091/mbc.e12-06-0450

Cited by 16 publications

(15 citation statements)

References 111 publications

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“…To study the effect of stress granule-associated mutant-FUS on the dynamic properties of stress granules, we employed fluorescence recovery after photobleaching (FRAP). FRAP measures the relative kinetics and affinities of protein binding within complexes, such as stress granules, over the time course of the experiment [44,45]. Because FRAP reports on binding events in live cells, fluorescently tagged-proteins were employed for these experiments [32,42,43,46].…”

Section: Resultsmentioning

confidence: 99%

“…FRAP experiments were performed at 37°C as previously described [45]. Multiple cells were analyzed in each experiment over a 30 min period starting at 60 min of sodium arsenite exposure.…”

Section: Methodsmentioning

confidence: 99%

“…The data was analyzed and background fluorescence subtracted using Excel. The relative fluorescence intensity (I rel ) in the bleached area was calculated as previously shown [45]. Briefly, the following equation was used: I rel, t = (I t × (C 0 /C t ))-(I pbl × (C 0 /C bl ))/(I 0 -(I pbl × (C 0 /C pbl )), where C 0 is the total cellular fluorescence before bleaching, C pbl is the total cellular fluorescence in the post-bleach image, C t is the total cellular fluorescence at time t, I 0 is the pre-bleach ROI fluorescence intensity, I t is the ROI fluorescence intensity at time t, and I pbl is the post-bleach ROI fluorescence intensity.…”

Section: Methodsmentioning

confidence: 99%

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Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics

Baron

Kaushansky

Ward

et al. 2013

Mol Neurodegeneration

131

115

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BackgroundAmyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress. Since only the mutants, but not the endogenous wild-type FUS, are associated with stress granules under most of the stress conditions reported to date, the relationship between FUS and stress granules represents a mutant-specific phenotype and thus may be of significance in mutant-induced pathogenesis. While the association of mutant-FUS with stress granules is well established, the effect of the mutant protein on stress granules has not been examined. Here we investigated the effect of mutant-FUS on stress granule formation and dynamics under conditions of oxidative stress.ResultsWe found that expression of mutant-FUS delays the assembly of stress granules. However, once stress granules containing mutant-FUS are formed, they are more dynamic, larger and more abundant compared to stress granules lacking FUS. Once stress is removed, stress granules disassemble more rapidly in cells expressing mutant-FUS. These effects directly correlate with the degree of mutant-FUS cytoplasmic localization, which is induced by mutations in the nuclear localization signal of the protein. We also determine that the RGG domains within FUS play a key role in its association to stress granules. While there has been speculation that arginine methylation within these RGG domains modulates the incorporation of FUS into stress granules, our results demonstrate that this post-translational modification is not involved.ConclusionsOur results indicate that mutant-FUS alters the dynamic properties of stress granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in stress granule assembly and cellular stress response.

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Section: Resultsmentioning

confidence: 99%

“…FRAP experiments were performed at 37°C as previously described [45]. Multiple cells were analyzed in each experiment over a 30 min period starting at 60 min of sodium arsenite exposure.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics

Baron

Kaushansky

Ward

et al. 2013

Mol Neurodegeneration

131

115

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“…The AKT signaling pathway regulates the assembly of the core EJC proteins eIF4A3, MAGOH, and Y14 into complexes at speckled domains, which is essential for mRNA export. AKT inhibition results in the disorder of mRNA export and gene expression [41]. REF1/Aly is a nuclear speckle protein implicated in mRNA export and is a physiological target of the nuclear Akt signaling cascade [42,43].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

ITRAQ-Based Proteomics Analysis of Triptolide On Human A549 Lung Adenocarcinoma Cells

Zhao

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Triptolide (TP) is a diterpenoid triepoxide extracted from the traditional Chinese medical herb Tripterygium wilfordii that exerts prominent broad-spectrum anticancer activity to repress proliferation and induce cancer cell apoptosis through various molecular pathways. We previously observed that TP inhibits the progression of A549 cells and pancreatic cancer cells (PNCA-1) in vitro. However, the complex molecular mechanism underlying the anticancer activity of TP is not well understood. Methods: To explore the molecular mechanisms by which TP induces lung cancer cell apoptosis, we investigated changes in the protein profile of A549 cells treated with TP using a proteomics approach (iTRAQ [isobaric tags for relative and absolute quantitation] combined with NanoLC-MS/MS [nano liquid chromatographymass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools OmicsBean and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and were verified using western blotting. Apoptosis and cell cycle effects were analyzed using flow cytometry. Results: TP induced apoptosis in A549 cells and blocked A549 cells at the G2/M phase. Using iTRAQ technology, we observed 312 differentially expressed proteins associated in networks and implicated in different KEGG pathways. Gene Ontology (GO) analysis showed the overviews of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Moreover, some candidate proteins involved in PARP1/AIF and nuclear Akt signaling pathways or metastasis processes were validated by western blotting. Conclusion: TP exerted anti-tumor activity on non-small cell lung cancer (NSCLC) A549 lung adenocarcinoma cells by dysregulating tumor-related protein expression. Herein, we provide a preliminary study of TP-related cytotoxicity on A549 cells using proteomics tools. These findings may improve the current understanding of the anti-tumor effects of TP on lung cancer cells and may reveal candidate proteins as potential targets for the treatment of lung cancer.

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“…Some RNAs (mRNAs) are then processed, transported to the cytoplasm, 5,6 and translated into proteins. RNA polymerase I synthesizes RNAs ribosomal RNAs (rRNAs)—the first known noncoding RNAs (ncRNAs), which are required for protein synthesis.…”

Section: Coding and Non-coding Rnasmentioning

confidence: 99%

Long Noncoding RNAs in the Pathogenesis of Barrett’s Esophagus and Esophageal Carcinoma

Abraham

Meltzer

2017

Gastroenterology

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For many years, only a small fraction of the human genome was believed to regulate cell function and development. This protein-coding portion composed only 1% to 2% of 3 billion human DNA base pairs— the remaining sequence was classified as junk DNA. Subsequent research has revealed that most of the genome is transcribed into a broad array of noncoding RNAs, ranging in size from microRNA (20–23 nucleotides) to long noncoding RNA (lncRNA, more than 200 nucleotides). These noncoding RNA classes have been shown to use diverse molecular mechanisms to control gene expression and organ system development. As anticipated, alterations in this large control system can contribute to disease pathogenesis and carcinogenesis. We review the involvement of noncoding RNAs—lncRNAs in particular—in development of Barrett's esophagus and esophageal carcinoma.

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Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway

Cited by 16 publications

References 111 publications

Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics

Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics

ITRAQ-Based Proteomics Analysis of Triptolide On Human A549 Lung Adenocarcinoma Cells

Long Noncoding RNAs in the Pathogenesis of Barrett’s Esophagus and Esophageal Carcinoma

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