scholarly journals Gene expression and phenotypic characterization of mouse heart after chronic constant or intermittent hypoxia

2005 ◽  
Vol 22 (3) ◽  
pp. 292-307 ◽  
Author(s):  
Chenhao Fan ◽  
Dumitru A. Iacobas ◽  
Dan Zhou ◽  
Qiaofang Chen ◽  
James K. Lai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Development ◽  
Intermittent Hypoxia ◽  
Molecular Mechanisms ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Phenotypic Characterization ◽  
Mouse Heart ◽  
Eukaryotic Translation ◽  
Protein Levels

Chronic constant hypoxia (CCH), such as in pulmonary diseases or high altitude, and chronic intermittent hypoxia (CIH), such as in sleep apnea, can lead to major changes in the heart. Molecular mechanisms underlying these cardiac alterations are not well understood. We hypothesized that changes in gene expression could help to delineate such mechanisms. The current study used a neonatal mouse model in CCH or CIH combined with cDNA microarrays to determine changes in gene expression in the CCH or CIH mouse heart. Both CCH and CIH induced substantial alterations in gene expression. In addition, a robust right ventricular hypertrophy and cardiac enlargement was found in CCH- but not in CIH-treated mouse heart. On one hand, upregulation in RNA and protein levels of eukaryotic translation initiation factor-2α and -4E (eIF-2α and eIF-4E) was found in CCH, whereas eIF-4E was downregulated in 1- and 2-wk CIH, suggesting that eIF-4E is likely to play an important role in the cardiac hypertrophy observed in CCH-treated mice. On the other hand, the specific downregulation of heart development-related genes (e.g., notch gene homolog-1, MAD homolog-4) and the upregulation of proteolysis genes (e.g., calpain-5) in the CIH heart can explain the lack of hypertrophy in CIH. Interestingly, apoptosis was enhanced in CCH but not CIH, and this was correlated with an upregulation of proapoptotic genes and downregulation of anti-apoptotic genes in CCH. In summary, our results indicate that 1) the pattern of gene response to CCH is different from that of CIH in mouse heart, and 2) the identified expression differences in certain gene groups are helpful in dissecting mechanisms responsible for phenotypes observed.

scholarly journals The exon junction complex core factor eIF4A3 is a key regulator of HPV16 gene expression

2021 ◽  
Vol 41 (4) ◽  
Author(s):  
Koceila Meznad ◽  
Philippe Paget-Bailly ◽  
Elise Jacquin ◽  
Anne Peigney ◽  
François Aubin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Exon Junction Complex ◽  
Eukaryotic Translation ◽  
Protein Levels ◽  
Exon Junction ◽  
Complex Core ◽  
Eukaryotic Translation Initiation ◽  
E6 And E7

Abstract High-risk human papillomavirus (hrHPVs), particularly HPV16 and HPV18, are the etiologic factors of ano-genital cancers and some head and neck squamous cell carcinomas (HNSCCs). Viral E6 and E7 oncoproteins, controlled at both transcriptional and post-transcriptional levels, drive hrHPVs-induced carcinogenesis. In the present study, we investigated the implication of the DEAD-box helicase eukaryotic translation initiation factor 4A3 (eIF4A3,) an Exon Junction Complex factor, in the regulation of HPV16 gene expression. Our data revealed that the depletion of the factor eIF4A3 up-regulated E7 oncoprotein levels. We also showed that the inhibition of the nonsense-mediated RNA decay (NMD) pathway, resulted in the up-regulation of E7 at both RNA and protein levels. We therefore proposed that HPV16 transcripts might present different susceptibilities to NMD and that this pathway could play a key role in the levels of expression of these viral oncoproteins during the development of HPV-related cancers.

scholarly journals The Cap-Binding Complex CBC and the Eukaryotic Translation Factor eIF4E: Co-Conspirators in Cap-Dependent RNA Maturation and Translation

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6185
Author(s):  
Jean-Clement Mars ◽  
Mehdi Ghram ◽  
Biljana Culjkovic-Kraljacic ◽  
Katherine L. B. Borden
Keyword(s):  
Nuclear Export ◽  
Mammalian Cells ◽  
Physical Nature ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Cell Physiology ◽  
Eukaryotic Translation ◽  
Protein Levels ◽  
Cap Binding Complex ◽  
Rna Maturation

The translation of RNA into protein is a dynamic process which is heavily regulated during normal cell physiology and can be dysregulated in human malignancies. Its dysregulation can impact selected groups of RNAs, modifying protein levels independently of transcription. Integral to their suitability for translation, RNAs undergo a series of maturation steps including the addition of the m7G cap on the 5′ end of RNAs, splicing, as well as cleavage and polyadenylation (CPA). Importantly, each of these steps can be coopted to modify the transcript signal. Factors that bind the m7G cap escort these RNAs through different steps of maturation and thus govern the physical nature of the final transcript product presented to the translation machinery. Here, we describe these steps and how the major m7G cap-binding factors in mammalian cells, the cap binding complex (CBC) and the eukaryotic translation initiation factor eIF4E, are positioned to chaperone transcripts through RNA maturation, nuclear export, and translation in a transcript-specific manner. To conceptualize a framework for the flow and integration of this genetic information, we discuss RNA maturation models and how these integrate with translation. Finally, we discuss how these processes can be coopted by cancer cells and means to target these in malignancy.

YAP-Induced Endothelial-Mesenchymal Transition in Oral Submucous Fibrosis

2019 ◽  
Vol 98 (8) ◽  
pp. 920-929 ◽  
Author(s):  
J. Li ◽  
M. Yao ◽  
X. Zhu ◽  
Q. Li ◽  
J. He ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Oral Submucous Fibrosis ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Mesenchymal Transition ◽  
Eukaryotic Translation ◽  
Initiation Factor 2 ◽  
Potentially Malignant ◽  
Submucous Fibrosis ◽  
Mesenchymal Transformation

Oral submucous fibrosis (OSF) is a potentially malignant disorder. Current studies have shown that chewing areca nut is considered the main cause of OSF, and endothelial-mesenchymal transformation (EndMT) participates in the occurrence and development of the fibrotic lesion. However, the specific molecular mechanisms and treatments remain unclear. Here, we report the mechanism of arecoline-induced EndMT and the importance of this mechanism in OSF, and we also identify potential therapeutics for decreasing OSF incidence. We demonstrate the overexpression of Yes-associated protein (YAP) in human samples and that it was significantly associated with OSF pathologic stage. Arecoline activated YAP by increasing reactive oxygen species levels and inducing the PERK pathway (eukaryotic translation initiation factor 2 alpha kinase 3), resulting in the initiation of EndMT and leading to OSF. Verteporfin, a YAP–TEA domain pathway inhibitor, suppressed EndMT and decreased collagen accumulation, resulting in the alleviation of OSF in mice. These data indicate that arecoline regulates the activity of YAP and highlight an alternative method for treating OSF.

scholarly journals Human eIF3: from ‘blobology’ to biological insight

2017 ◽  
Vol 372 (1716) ◽  
pp. 20160176 ◽  
Author(s):  
Jamie H. D. Cate
Keyword(s):  
Translation Initiation ◽  
Molecular Mechanisms ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Messenger Rnas ◽  
Internal Ribosome Entry ◽  
General Role ◽  
Eukaryotic Translation ◽  
Biological Insight ◽  
Eukaryotic Translation Initiation

Translation in eukaryotes is highly regulated during initiation, a process impacted by numerous readouts of a cell's state. There are many cases in which cellular messenger RNAs likely do not follow the canonical ‘scanning’ mechanism of translation initiation, but the molecular mechanisms underlying these pathways are still being uncovered. Some RNA viruses such as the hepatitis C virus use highly structured RNA elements termed internal ribosome entry sites (IRESs) that commandeer eukaryotic translation initiation, by using specific interactions with the general eukaryotic translation initiation factor eIF3. Here, I present evidence that, in addition to its general role in translation, eIF3 in humans and likely in all multicellular eukaryotes also acts as a translational activator or repressor by binding RNA structures in the 5′-untranslated regions of specific mRNAs, analogous to the role of the mediator complex in transcription. Furthermore, eIF3 in multicellular eukaryotes also harbours a 5′ 7-methylguanosine cap-binding subunit—eIF3d—which replaces the general cap-binding initiation factor eIF4E in the translation of select mRNAs. Based on results from cell biological, biochemical and structural studies of eIF3, it is likely that human translation initiation proceeds through dozens of different molecular pathways, the vast majority of which remain to be explored. This article is part of the themed issue ‘Perspectives on the ribosome’.

scholarly journals Global Gene Expression Profiling Reveals Widespread yet Distinctive Translational Responses to Different Eukaryotic Translation Initiation Factor 2B-Targeting Stress Pathways

2005 ◽  
Vol 25 (21) ◽  
pp. 9340-9349 ◽  
Author(s):  
Julia B. Smirnova ◽  
Julian N. Selley ◽  
Fatima Sanchez-Cabo ◽  
Kathleen Carroll ◽  
A. Alan Eddy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Translation Initiation ◽  
Translational Control ◽  
Stress Conditions ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Eukaryotic Translation Initiation

ABSTRACT Global inhibition of protein synthesis is a hallmark of many cellular stress conditions. Even though specific mRNAs defy this (e.g., yeast GCN4 and mammalian ATF4), the extent and variation of such resistance remain uncertain. In this study, we have identified yeast mRNAs that are translationally maintained following either amino acid depletion or fusel alcohol addition. Both stresses inhibit eukaryotic translation initiation factor 2B, but via different mechanisms. Using microarray analysis of polysome and monosome mRNA pools, we demonstrate that these stress conditions elicit widespread yet distinct translational reprogramming, identifying a fundamental role for translational control in the adaptation to environmental stress. These studies also highlight the complex interplay that exists between different stages in the gene expression pathway to allow specific preordained programs of proteome remodeling. For example, many ribosome biogenesis genes are coregulated at the transcriptional and translational levels following amino acid starvation. The transcriptional regulation of these genes has recently been connected to the regulation of cellular proliferation, and on the basis of our results, the translational control of these mRNAs should be factored into this equation.

scholarly journals The Protein Expression of PDL1 Is Highly Correlated with Those of eIF2α and ATF4 in Lung Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Liang-Che Chang ◽  
Tzu-Ping Chen ◽  
Wei-Ke Kuo ◽  
Chung-Ching Hua
Keyword(s):  
Lung Cancer ◽  
Protein Level ◽  
Cell Function ◽  
Immune Cell ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation ◽  
Protein Levels ◽  
Tumor Tissues ◽  
Programmed Death

Introduction. The expression of programmed death 1 (PD1) and programmed death ligand 1 (PDL1) can be induced by the interferon (IFN)/signal transducer and activator of transcription (STAT) pathway. The PD1/PDL1 reverse signaling can activate the eukaryotic translation initiation factor 2 (eIF2α)/activating transcription factor 4 (ATF4) pathway which in turn regulates the expression of IFN regulatory factor (IRF) 7 and IFNα. The eIF2α/ATF4 pathway is responsible for the integrated stress response (ISR) of unfolded protein response (UPR) which can affect immune cell function in tumor microenvironment. Materials and Methods. The protein levels of PDL1, IRF1, IRF7, STAT1, STAT2, IFNAR1, eIF2α, and ATF4 in the normal and tumor tissues of 27 subjects with lung cancer were determined by Western blot. Results. The protein level of PDL1 was significantly correlated with those of IRF1, eIF2α, and ATF4 in the tissues of all subjects and the subgroup of squamous cell carcinoma but not in the normal tissue of adenocarcinoma. The protein levels of IRF1, eIF2α, and ATF4 were consistently correlated in the tumor tissues but to various extents in the normal ones. The protein level of PDL1 was not correlated with those of STAT1 and STAT2 in all the tissues. Conclusion. The PDL1 expression in lung cancer may be independent of STAT1 and STAT2. The PD1/PDL1 axis and UPR/ISR may be closely associated in the tumor tissues of lung cancer.

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