The eEF1 family of mammalian translation elongation factors

Negrutskii, B. S.; Shalak, V. F.; Novosylna, O. V.; Porubleva, L. V.; Lozhko, D. M.; El’skaya, A. V.

doi:10.1016/j.bbadva.2022.100067

Cited by 11 publications

(10 citation statements)

References 100 publications

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“…Finally, an obvious choice for inclusion in this evaluation is Krt3, the other corneal-specific cytokeratin. For genes that could be expected to remain invariant, the selection included (a) EEFA1 and E1F1, two highly expressed genes that play critical but distinct roles in the efficiency and/or accuracy of translation [ 32 , 33 ], and the genes commonly chosen as constancy controls, ACTG1, ACTB, and GAPDH.…”

Section: Resultsmentioning

confidence: 99%

A Keratin 12 Expression-Based Analysis of Stem-Precursor Cells and Differentiation in the Limbal–Corneal Epithelium Using Single-Cell RNA-Seq Data

Wolosin

2024

Biology

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The corneal epithelium (CE) is spread between two domains, the outer vascularized limbus and the avascular cornea proper. Epithelial cells undergo constant migration from the limbus to the vision-critical central cornea. Coordinated with this migration, the cells undergo differentiation changes where a pool of unique stem/precursor cells at the limbus yields the mature cells that reach the corneal center. Differentiation is heralded by the expression of the corneal-specific Krt12. Processing data acquired by scRNA-Seq showed that the increase in Krt12 expression occurs in four distinct steps within the limbus, plus a single continuous increase in the cornea. Differential gene analysis demonstrated that these domains reflect discreet stages of CE differentiation and yielded extensive information of the genes undergoing down- or upregulation in the sequential transition from less to more differentiate conditions. The approach allowed the identification of multiple gene cohorts, including (a) the genes which have maximal expression in the most primitive, Krt12-negative cell cohort, which is likely to include the stem/precursor cells; (b) the sets of genes that undergo continuous increase or decrease along the whole differentiation path; and (c) the genes showing maximal positive or negative correlation with the changes in Krt12.

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Section: Resultsmentioning

confidence: 99%

A Keratin 12 Expression-Based Analysis of Stem-Precursor Cells and Differentiation in the Limbal–Corneal Epithelium Using Single-Cell RNA-Seq Data

Wolosin

2024

Biology

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“…“Eukaryotic translation elongation” was also significantly associated with the upregulated EEF1G in MS17-treated SW620 cells. EEF1G is part of the elongation factor-1 complex that delivers aminoacyl-tRNA and amino acids to the ribosome during the elongation step in gene translation [ 242 ]. EEF1G has been reported to be overexpressed in multiple cancers, including CRC, but little is known about its potential roles in cancer progression [ 243 , 244 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Cancer Mechanisms of Diarylpentanoid MS17 (1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in Human Colon Cancer Cells: A Proteomics Approach

Hon,

Zainal Abidin,

Abas

et al. 2024

IJMS

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Diarylpentanoids are synthesized to overcome curcumin’s poor bioavailability and low stability to show enhanced anti-cancer effects. Little is known about the anti-cancer effects of diarylpentanoid MS17 (1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in colon cancer cells. This study aimed to elucidate molecular mechanisms and pathways modulated by MS17 in colon cancer based on proteomic profiling of primary SW480 and metastatic SW620 colon cancer cells. Cytotoxicity and apoptotic effects of MS17 were investigated using MTT assay, morphological studies, and Simple Western analysis. Proteomic profiling using LC/MS analysis identified differentially expressed proteins (DEPs) in MS17-treated cells, with further analysis in protein classification, gene ontology enrichment, protein–protein interaction network and Reactome pathway analysis. MS17 had lower EC50 values (SW480: 4.10 µM; SW620: 2.50 µM) than curcumin (SW480: 17.50 µM; SW620: 13.10 µM) with a greater anti-proliferative effect. MS17 treatment of 1× EC50 induced apoptotic changes in the morphology of SW480 and SW620 cells upon 24 h treatment. A total of 24 and 92 DEPs (fold change ≥ 1.50) were identified in SW480 and SW620 cells, respectively, upon MS17 treatment of 2× EC50 for 24 h. Pathway analysis showed that MS17 may induce its anti-cancer effects in both cells via selected DEPs associated with the top enriched molecular pathways. RPL and RPS ribosomal proteins, heat shock proteins (HSPs) and ubiquitin–protein ligases (UBB and UBC) were significantly associated with cellular responses to stress in SW480 and SW620 cells. Our findings suggest that MS17 may facilitate the anti-proliferative and apoptotic activities in primary (SW480) and metastatic (SW620) human colon cancer cells via the cellular responses to stress pathway. Further investigation is essential to determine the alternative apoptotic mechanisms of MS17 that are independent of caspase-3 activity and Bcl-2 protein expression in these cells. MS17 could be a potential anti-cancer agent in primary and metastatic colon cancer cells.

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“…p-eEF1Bα (Ser106) bound to the promoter of mTOR and activated its gene transcription. Previous reports have shown that some eEFs, including eEF1A1, eEF1Bδ, and eEF1Bγ, can enter the nucleus to regulate gene transcription. − It has not been reported that the nonclassical function of eEF1Bα is beyond translation. To the best of our knowledge, this is the first report that eEF1Bα can enter the nucleus and play a regulatory role in gene transcription.…”

Section: Discussionmentioning

confidence: 99%

“…Several previous studies have shown that some eEFs have noncanonical functions beyond translation, and some of them can play a role in the nucleus. , After acetylation, eEF1A1 enters the nucleus, binds the transcription factor Sox10, and inhibits its target gene transcription . eEF1Bδ can generate a transcription factor that binds to the heat shock element in the nucleus through mRNA alternative splicing .…”

Section: Introductionmentioning

confidence: 99%

Methionine and Leucine Promote mTOR Gene Transcription and Milk Synthesis in Mammary Epithelial Cells through the eEF1Bα-UBR5-ARID1A Signaling

Qi,

Yu,

Fan

et al. 2024

J. Agric. Food Chem.

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Amino acids are essential for the activation of the mechanistic target of rapamycin (mTOR), but the corresponding molecular mechanism is not yet fully understood. We previously found that Met stimulated eukaryotic elongation factor α (eEF1Bα) nuclear localization in bovine mammary epithelial cells (MECs). Herein, we explored the role and molecular mechanism of eEF1Bα in methionine (Met)-and leucine (Leu)-stimulated mTOR gene transcription and milk synthesis in MECs. eEF1Bα knockdown decreased milk protein and fat synthesis, cell proliferation, and mTOR mRNA expression and phosphorylation, whereas eEF1Bα overexpression had the opposite effects. QE-MS analysis detected that eEF1Bα was phosphorylated at Ser106 in the nucleus and Met and Leu stimulated p-eEF1Bα nuclear localization. eEF1Bα knockdown abrogated the stimulation of Met and Leu by mTOR mRNA expression and phosphorylation, and this regulatory role was dependent on its phosphorylation. Akt knockdown blocked the stimulation of Met and Leu by eEF1Bα and p-eEF1Bα expression. ChIP-PCR detected that p-eEF1Bα bound only to the −548 to −793 nt site in the mTOR promoter, and ChIP-qPCR further detected that Met and Leu stimulated this binding. eEF1Bα mediated Met and Leu' stimulation on mTOR mRNA expression and phosphorylation through inducing AT-rich interaction domain 1A (ARID1A) ubiquitination degradation, and this process depended on eEF1Bα phosphorylation. p-eEF1Bα interacted with ARID1A and ubiquitin protein ligase E3 module N-recognition 5 (UBR5), and UBR5 knockdown rescued the decrease of the ARID1A protein level by eEF1Bα overexpression. Both eEF1Bα and p-eEF1Bα were highly expressed in mouse mammary gland tissues during the lactating period. In summary, we reveal that Met and Leu stimulate mTOR transcriptional activation and milk protein and fat synthesis in MECs through eEF1Bα-UBR5-ARID1A signaling.

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The eEF1 family of mammalian translation elongation factors

Cited by 11 publications

References 100 publications

A Keratin 12 Expression-Based Analysis of Stem-Precursor Cells and Differentiation in the Limbal–Corneal Epithelium Using Single-Cell RNA-Seq Data

A Keratin 12 Expression-Based Analysis of Stem-Precursor Cells and Differentiation in the Limbal–Corneal Epithelium Using Single-Cell RNA-Seq Data

Anti-Cancer Mechanisms of Diarylpentanoid MS17 (1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in Human Colon Cancer Cells: A Proteomics Approach

Methionine and Leucine Promote mTOR Gene Transcription and Milk Synthesis in Mammary Epithelial Cells through the eEF1Bα-UBR5-ARID1A Signaling

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