Up-regulation of Translation Eukaryotic Initiation Factor 4E in Nucleophosmin 1 Haploinsufficient Cells Results in Changes in CCAAT Enhancer-binding Protein α Activity

Khanna-Gupta, Arati; Abayasekara, Nirmalee; Levine, Marshall; Sun, Hong; Virgilio, Maria; Nia, Navid; Halene, Stephanie; Sportoletti, Paolo; Jeong, Jee‐Yeong; Pandolfi, Pier Paolo; Berliner, Nancy

doi:10.1074/jbc.m112.373274

Cited by 17 publications

(19 citation statements)

References 42 publications

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“…For instance, eIF4E is a direct NF‐κB target which is dysregulated in M4/M5 AML . Other groups have shown that eIF4E is also a target of C/EBP . Furthermore, eIF4E mRNA stability is elevated by the HuR protein and is destabilized by AUF1 .…”

Section: Dysregulation Of Eif4e Levelsmentioning

confidence: 99%

The eukaryotic translation initiation factor eIF4E in the nucleus: taking the road less traveled

Osborne

Borden

2014

Immunological Reviews

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Summary The eukaryotic translation initiation factor eIF4E is a potent oncogene. Although eIF4E has traditional roles in translation initiation in the cytoplasm, it is also found in the nucleus, suggesting that it has activities beyond its role in protein synthesis. The road less traveled has been taken to study these nuclear activities and to understand their contribution to the oncogenic potential of eIF4E. The molecular features and biological pathways underpinning eIF4E’s nuclear mRNA export are described. New classes of eIF4E regulators have been identified and their relevance to cancer shown. The studies presented here reveal the molecular, biophysical, and structural bases for eIF4E regulation. Finally, recent clinical work targeting eIF4E in acute myeloid leukemia patients with ribavirin is discussed. In summary, these findings provide a novel paradigm for eIF4E function and the molecular basis for targeting it in leukemia patients.

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Section: Dysregulation Of Eif4e Levelsmentioning

confidence: 99%

The eukaryotic translation initiation factor eIF4E in the nucleus: taking the road less traveled

Osborne

Borden

2014

Immunological Reviews

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“…Others acquire altered properties such as sodium permeability for the N‐terminally truncated form of the potassium channel, subfamily K, member 2 (K2P2.1), which changes neuron responsiveness in specific rat brain tissues and developmental stages . Alternative translation initiation can also cause a loss of function, such as the dominant negative effect of truncated CCAAT/enhancer binding protein beta (C/EBP β) , or can functionally modulate growth factors and oncogenes (including fibroblast growth factor (FGF) , vascular endothelial growth factor (VEGF) , and V‐myc avian myelocytomatosis viral oncogene homolog (c‐Myc) ). Moreover, N‐terminal proteoforms may have different cellular stabilities as is the case for the opioid receptor mu 1 (OPRM1) .…”

Section: Alternative Translation Increases the Complexity Of Eukaryotmentioning

confidence: 99%

The proteome under translational control

2014

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A single eukaryotic gene can give rise to a variety of protein forms (proteoforms) as a result of genetic variation and multilevel regulation of gene expression. In addition to alternative splicing, an increasing line of evidence shows that alternative translation contributes to the overall complexity of proteomes. Identifying the repertoire of proteins and micropeptides expressed by alternative selection of (near-)cognate translation initiation sites and different reading frames however remains challenging with contemporary proteomics. MS-enabled identification of proteoforms is expected to benefit from transcriptome and translatome data by the creation of customized and sample-specific protein sequence databases. Here, we focus on contemporary integrative omics approaches that complement proteomics with DNA- and/or RNA-oriented technologies to elucidate the mechanisms of translational control. Together, these technologies enable to map the translation (initiation) landscape and more comprehensively define the inventory of proteoforms raised upon alternative translation, thus assisting in the (re-)annotation of genomes.

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“…The formation and function of the EIF4F complex need to be tightly regulated to maintain the cellular homeostasis. Some major signal transduction pathways (e.g., PI3K/Akt/mTOR or MAPK) [ 28 – 30 ] and transcription factors (e.g., MYC or C/EBPα) have been shown to regulate the EIF4F complex [ 31 , 32 ]. In NSCLC, the rapamycin mediated inhibition of mTOR signaling can increase the phosphorylation of both Akt and EIF4E through a negative feedback mechanism, while the PI3K inhibitors such as LY294002 can reverse such undesirable effects [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting EIF4F complex in non-small cell lung cancer cells

et al. 2017

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Non-small cell lung cancer (NSCLC) accounts for about 85–90% of lung cancer cases, which represents the leading cause of cancer-related death in the world. The majority of lung cancer patients doesn't respond well to conventional chemo-/radio-therapeutic regimens and have a poor prognosis. The recent introduction of targeted therapy and immunotherapy gives new hopes to NSCLC patients, but their outcome/prognosis is far from satisfactory. The translation initiation EIF4F complex has been shown to play important roles in cancer progression, but its functional role and therapeutic effect in lung cancers especially NSCLC remain largely unknown. In this current review, we summarize recent findings regarding the role of EIF4F complex in NSCLC progression and targeted therapy potentials. We also discuss the unanswered questions and future directions in this field.

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Up-regulation of Translation Eukaryotic Initiation Factor 4E in Nucleophosmin 1 Haploinsufficient Cells Results in Changes in CCAAT Enhancer-binding Protein α Activity

Abstract: Background: Myeloid cell lines were generated from Npm1 ϩ/Ϫ mice to understand the role of NPM1 in MDS.

Cited by 17 publications

References 42 publications

The eukaryotic translation initiation factor eIF4E in the nucleus: taking the road less traveled

The eukaryotic translation initiation factor eIF4E in the nucleus: taking the road less traveled

The proteome under translational control

Targeting EIF4F complex in non-small cell lung cancer cells

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