4E-BP1 as an oncotarget

She, Qing-Bai

doi:10.18632/aging.100794

Cited by 4 publications

(4 citation statements)

References 7 publications

(6 reference statements)

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“…Moreover, stimulation of eIF4F-mediated translation initiation is modulated by either directly altering the expression of phosphorylation of its components or through regulation of its formation and activity which is tightly controlled to maintain cellular and tissue homeostasis. Finally, the dynamic equilibrium between eIF4E and 4E-BP1 is important because hyperphosphorylated 4E-BP1 favors eIF4E stimulated cap-dependent translation, while 4E-BP1 hypophosphorylation stabilizes the binding to eIF4E and suppression of translation, thus favoring IRES-dependent translation initiation [189].…”

Section: Translation Regulation In Skin Tissue Homeostasis and Neoplastic Transformationmentioning

confidence: 99%

Translation regulation in skin cancer from a tRNA point of view

Grafanaki

Anastasakis²,

Kyriakopoulos

et al. 2019

Epigenomics

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Protein synthesis is a central and dynamic process, frequently deregulated in cancer through aberrant activation or expression of translation initiation factors and tRNAs. The discovery of tRNA-derived fragments, a new class of abundant and, in some cases stress-induced, small noncoding RNAs has perplexed the epigenomics landscape and highlights the emerging regulatory role of tRNAs in translation and beyond. Skin is the biggest organ in human body, which maintains homeostasis of its multilayers through regulatory networks that induce translational reprogramming, and modulate tRNA transcription, modification and fragmentation, in response to various stress signals, like UV irradiation. In this review, we summarize recent knowledge on the role of translation regulation and tRNA biology in the alarming prevalence of skin cancer.

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Section: Translation Regulation In Skin Tissue Homeostasis and Neoplastic Transformationmentioning

confidence: 99%

Translation regulation in skin cancer from a tRNA point of view

Grafanaki

Anastasakis²,

Kyriakopoulos

et al. 2019

Epigenomics

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show abstract

Section: Introductionmentioning

confidence: 99%

“…Eukaryotic translation initiation factor 4E (eIF4E) is an important component of the transcription initiation complex, which can control mRNAs that generally encode proteins involved in cellular growth and survival. 5 4E‐BP1 is one of the inhibitory binding proteins, and it can combine with eIF4E to block its complex assembly and translation, which leads to inhibit the cell growth and survival. 6 It has been reported that 4E‐BP1 is a key regulatory element integrating the P3K/AKT and RAS/RAF/MEK/ERK pathways for oncogenic signaling, which can participate in tumor progress and metastasis.…”

Section: Introductionmentioning

confidence: 99%

The expression and significance of p4E‐BP1/4E‐BP1 in prostate cancer

Wang

2022

Clinical Laboratory Analysis

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Background Although the phosphorylation of 4E‐BP1 that has been detected in high‐grade prostate cancer has been reported in previous studies, overexpression of p4E‐BP1 and 4EBP1 and their clinical significance in prostate cancer still remain unknown. Methods One hundred six samples of prostate tissues were collected and analyzed by immunohistochemistry with p4E‐BP1 or 4E‐BP1 specific antibodies. Everolimus was used to block the phosphorylation of p4E‐BP1, and then flow cytometry, clone formation, transwell, and wound healing assays were performed to detect the survival and invasive ability of the prostate cancer cells. Results We found that the expression of 4E‐BP1 and p4E‐BP1 was higher in prostate cancer tissues than in normal tissues. Interestingly, the expression of p4E‐BP1 was significantly associated with Gleason score and lymph node metastasis, but had no obvious correlation with PSA and the presence of bone or visceral metastasis. However, no evident correlation was found between the positive expression of 4E‐BP1 and these clinical characteristics. In in vitro experiments, we found similar results as the clinical presentation that 4E‐BP1 and p4E‐BP1 were low expressed in normal prostate epithelial cells, but in prostate cancer cells, as the malignancy increasing, 4E‐BP1 and p4E‐BP1 expression also gradually increased. Then, we used Everolimus to inhibit the phosphorylation of 4E‐BP1 and found that Everolimus effectively reduced cloning formation, inhibited cell migration, and promoted apoptosis in a dose‐dependent manner in PC3 cells. Conclusions These findings suggest that p4E‐BP1 is a potential biomarker and therapy target for prostate cancer, and patients with high expressions of p4E‐BP1 may benefit from Everolimus treatment.

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“…4EBP1 inhibits protein synthesis by binding to eIF4E. Dephosphorylated active 4EBP1 binds to eukaryotic translation initiation factor 4E (eIF4E) and disrupts the formation of the cap-dependent translation initiation complex, comprising the eIF4A RNA helicase, the eIF4E mRNA cap-binding protein, and the eIF4G scaffolding protein, which is essential for protein synthesis and is associated with cancer development and progression [ 2 ]. When 4EBP1 is phosphorylated and deactivated by upstream signals at several sites (Thr37/46, Thr70, Ser65, etc.…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of the prognostic value of p-4EBP1 in human malignancies

Zhang

Guo

et al. 2017

Oncotarget

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Phosphorylated 4E-binding protein 1 (p-4EBP1) is the inactivated form of 4EBP1, which is a downstream mediator in the mTOR signaling pathway and a vital factor in the synthesis of some oncogenic proteins. This meta-analysis was conducted to assess the predicative value of p-4EBP1 expression in human malignancies. The PubMed and Embase databases were carefully searched. Articles comparing the prognostic worthiness of different p-4EBP1 levels in human malignancies were collected for pooled analyses and methodologically appraised using the Newcastle-Ottawa Scale (NOS). A total of 39 retrospective cohorts with an overall sample size of 3,980 were selected. Patients with lower p-4EBP1 expression had better 3-year (P < 0.00001), 5-year (P < 0.00001), and 10-year (P = 0.03) overall survival and better 3-year (P < 0.0001) and 5-year (P = 0.0005) disease-free survival. Subgroup analyses confirmed the unfavorable prognosis associated with p-4EBP1 overexpression. These findings were further validated by sensitivity analyses. Harbord and Peters tests revealed no publication bias within the included studies. It thus appears higher expression of p-4EBP1 indicates a poor prognosis in human malignancies.

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4E-BP1 as an oncotarget

Cited by 4 publications

References 7 publications

Translation regulation in skin cancer from a tRNA point of view

Translation regulation in skin cancer from a tRNA point of view

The expression and significance of p4E‐BP1/4E‐BP1 in prostate cancer

Meta-analysis of the prognostic value of p-4EBP1 in human malignancies

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