Muscarinic acetylcholine receptors regulate the dephosphorylation of eukaryotic translation elongation factor 2 in SNU-407 colon cancer cells

Vasamsetti, Bala Murali Krishna; Liu, Ziyu; Park, Yang-Seo; Cho, Nam Jeong

doi:10.1016/j.bbrc.2019.06.059

Cited by 7 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The eukaryotic elongation factor 2 (eEF2) mediates ribosomal translocation. 26 Its activity is inhibited by phosphorylation. S6K1 can enhance the activity of eEF2 by reducing its phosphorylation.…”

Section: Signaling Pathways Involved In Ribosome Biogenesismentioning

confidence: 99%

Ribosome biogenesis in disease: new players and therapeutic targets

Jiao

Liu

et al. 2023

Sig Transduct Target Ther

View full text Add to dashboard Cite

The ribosome is a multi-unit complex that translates mRNA into protein. Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation, differentiation, apoptosis, development, and transformation. The mTORC1, Myc, and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis. Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth. Myc is implicated in cancer development by enhancing RNA Pol II activity, leading to uncontrolled cancer cell growth. The deregulation of noncoding RNAs such as microRNAs, long noncoding RNAs, and circular RNAs is involved in developing blood, neurodegenerative diseases, and atherosclerosis. We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance. We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting, ribosome-stalling, and ribosome-collision. We summarize the role of ribosome biogenesis in the development of various diseases. Furthermore, we review the current clinical trials, prospective vaccines for COVID-19, and therapies targeting ribosome biogenesis in cancer, cardiovascular disease, aging, and neurodegenerative disease.

show abstract

Section: Signaling Pathways Involved In Ribosome Biogenesismentioning

confidence: 99%

Ribosome biogenesis in disease: new players and therapeutic targets

Jiao

Liu

et al. 2023

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…Further evidence from the current research that supports the notion that EDZ may disrupt protein synthesis in ZF is the enrichment of MAPK signaling in the KEGG pathway analysis (Figure 6). MAPK signaling enzymes play a significant role in the regulation of nucleosome and gene expression, mRNA stability, and translation [52][53][54]. MAPK signaling pathways are necessary for converting extracellular impulses into intracellular impulses to control cell proliferation, differentiation, survival, tissue regeneration, and organogenesis throughout the ZF life cycle [53][54][55].…”

Section: Discussionmentioning

confidence: 99%

“…MAPK signaling enzymes play a significant role in the regulation of nucleosome and gene expression, mRNA stability, and translation [52][53][54]. MAPK signaling pathways are necessary for converting extracellular impulses into intracellular impulses to control cell proliferation, differentiation, survival, tissue regeneration, and organogenesis throughout the ZF life cycle [53][54][55]. Certainly, more research is needed to fully appreciate the hypothesis that the disruption of protein synthesis is one of the causes of EDZ toxicity in ZF.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Profiling of Etridiazole-Exposed Zebrafish (Danio rerio) Embryos Reveals Pathways Associated with Cardiac and Ocular Toxicities

Vasamsetti,

Chon,

Yoon

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Etridiazole (EDZ) is a thiadiazole-containing fungicide commonly used to control Pythium and Phytophthora spp. Although previous studies have shown that EDZ is teratogenic, the exact molecular mechanisms underlying its toxicity remain unknown. In this study, a zebrafish (Danio rerio; ZF) model was used to explore the molecular pathways associated with EDZ toxicity. The whole transcriptome of ZF embryos exposed to 96 h of EDZ was analyzed, along with developmental abnormalities. EDZ-induced malformations were primarily related to the eyes, heart, and growth of the ZF. Compared to untreated ZF, etridiazole-treated ZF had 2882 differentially expressed genes (DEGs), consisting of 1651 downregulated genes and 1231 upregulated genes. Gene ontology enrichment analysis showed that DEGs were involved in biological processes, such as sensory perception, visual perception, sensory organ development, and visual system development, and showed transmembrane transporter and peptidase regulator activities. Metabolism, phototransduction, aminoacyl-tRNA biosynthesis, MAPK signaling pathway, calcium signaling pathway, and vascular smooth muscle contraction were among the most enriched KEGG pathways. The qPCR analyses of the eight random genes were in good agreement with the transcriptome data. These results suggest several putative mechanisms underlying EDZ-induced developmental deformities in ZF.

show abstract

“…The knockdown of ribosomal proteins, which are the key players in protein synthesis, leads to growth retardation and several other deformities in ZF. Moreover, Suzuki et al [20] reported that 1,2,4-thiadiazole derivatives modulate muscarinic acetylcholine receptors (mAChRs), which are known to modulate protein biosynthesis [21,22]. Therefore, it is plausible that the growth retardation and other deformities observed after EDZ exposure might be due to perturbations in protein biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Teratogenic and developmental toxic effects of etridiazole on zebrafish (Danio rerio) embryos

et al. 2020

Self Cite

View full text Add to dashboard Cite

Etridiazole (EDZ), a thiadiazole-containing toxic chemical, is widely used as a fungicide. Regular usage of EDZ may reach and contaminate water bodies, but its adverse effects on aquatic vertebrates have not been well studied. Therefore, the present study aimed to evaluate the harmful effects of EDZ using zebrafish (ZF) (Danio rerio) embryos. ZF embryos were treated with 3.75, 7.5, 15, 30, and 60 mg/L of EDZ. Subsequently, mortality and developmental toxicities were quantified at 24, 48, 72, and 96 h post fertilization (hpf). The results showed that embryo mortality was concentration- and time-dependent. The median lethal concentration (LC50) of EDZ at 96-h was 25.58 ± 1.49 mg/L. Besides, EDZ induced a series of morphological deformities, including abnormal somite formation, abnormal eye pigmentation, abnormal tail morphology, tail kinks, skeletal malformations (lordosis, kyphosis, and scoliosis), and yolk sac edema in a concentration-dependent manner. Among the deformities, the most significant were reduced heartbeat and increased incidence of pericardial edema. The median effective concentration (EC50) of EDZ at 96-h was 17.93 ± 2.22 mg/L and the 96-h teratogenic index (TI) value was 1.52. Taken together, these results indicate that EDZ is a teratogen, and primarily affects the cardiovascular system of ZF.

show abstract

Muscarinic acetylcholine receptors regulate the dephosphorylation of eukaryotic translation elongation factor 2 in SNU-407 colon cancer cells

Cited by 7 publications

References 24 publications

Ribosome biogenesis in disease: new players and therapeutic targets

Ribosome biogenesis in disease: new players and therapeutic targets

Transcriptome Profiling of Etridiazole-Exposed Zebrafish (Danio rerio) Embryos Reveals Pathways Associated with Cardiac and Ocular Toxicities

Teratogenic and developmental toxic effects of etridiazole on zebrafish (Danio rerio) embryos

Contact Info

Product

Resources

About