Binding of eEF1A2 to the RNA-dependent protein kinase PKR modulates its activity and promotes tumour cell survival

@article{Losada2018BindingOE,
  title={Binding of eEF1A2 to the RNA-dependent protein kinase PKR modulates its activity and promotes tumour cell survival},
  author={Alejandro Losada and Mar{\'i}a Jos{\'e} Mu{\~n}oz-Alonso and Marta Mart{\'i}nez-D{\'i}ez and Federico Gago and Juan Manuel Domínguez and Juan Fernando Mart{\'i}nez-Leal and Carlos M Galmarini},
  journal={British Journal of Cancer},
  year={2018},
  volume={119},
  pages={1410 - 1420}
}
BackgroundThrough several not-fully-characterised moonlighting functions, translation elongation factor eEF1A2 is known to provide a fitness boost to cancer cells. Furthermore, eEF1A2 has been demonstrated to confer neoplastic characteristics on preneoplastic, nontumourigenic precursor cells. We have previously shown that eEF1A2 is the target of plitidepsin, a marine drug currently in development for cancer treatment. Herein, we characterised a new signalling pathway through which eEF1A2… Expand
EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling
TLDR
Findings indicate that EEF1A2 represents a promising target in the treatment of aggressive LUAD and mediates the epithelial–mesenchymal transformation (EMT) to promote the metastasis of LUAD cells in vitro and in vivo. Expand
A rapid and specific method to simultaneously quantify eukaryotic elongation factor 1A1 and A2 protein levels in cancer cells.
TLDR
In cell western (ICW) is a valuable tool to specifically determine the intracellular level of eEF1A1-A2 proteins thus contributing to better define their role as potential therapeutic targets and prognostic markers in human tumors as well as for drug effects screening. Expand
Effect of activation of the Akt/mTOR signaling pathway by EEF1A2 on the biological behavior of osteosarcoma.
TLDR
There is high expression of EEF1A2 in OS, which can promote the proliferation, migration, and invasion of OS cells in vitro and the growth of OS tumors in vivo via activation of the Akt/mTOR signaling pathway. Expand
Expression pattern of EEF1A2 in brain tumors: Histological analysis and functional role as a promoter of EMT.
TLDR
EEF1A2 acts as an oncogene in both neuronal and glial cells and triggers an EMT program via PI3K pathway, which could explain the previously reported anomaly. Expand
Generation of endoplasmic reticulum stress and inhibition of autophagy by plitidepsin induces proteotoxic apoptosis in cancer cells.
TLDR
It is revealed that PLD induces an increase in the levels of misfolded proteins while simultaneously inhibiting the autophagic flux, which combined prevent PLD-treated cells from reducing proteotoxic stress and lead to apoptosis. Expand
Elevated levels of eEF1A2 protein expression in triple negative breast cancer relate with poor prognosis
TLDR
The data showed a negative prognostic role of eEF1A2 protein in TNBC, sustaining further investigations to confirm this result by wider and independent cohorts of patients. Expand
Tumor suppressor DRD2 facilitates M1 macrophages and restricts NF-κB signaling to trigger pyroptosis in breast cancer
TLDR
The critical role of DRD2 is revealed in educating M1 macrophages, restricting NF-κB signaling pathway and triggering different processes of programmed cell death in BrCa, revealing a predictive and therapeutic target for BrCa. Expand
LAIR-1 suppresses cell growth of ovarian cancer cell via the PI3K-AKT-mTOR pathway
TLDR
The findings suggest that LAIR-1 may suppress the growth of ovarian cancer cells by serving as a modulator that suppresses PI3K-AKT-mTOR directly or regulating protein synthesis at the translational level. Expand
Development of RNA binding proteins expression signature for prognosis prediction in gastric cancer patients.
TLDR
It was reported that the expression of RNA binding proteins (RBPs) in malignant tumors is dysregulated and is closely related to tumorigenesis, and this work systematically investigated the expression characteristics and clinical prognostic potential of these RBPs through bioinformatics methods. Expand
Crosstalks between inflammasome and autophagy in cancer
TLDR
Insight is provided into the mechanisms by which pathogen modulates the autophagy-inflammasome pathway to favor the infection-induced carcinogenesis and the emerging clinical efforts assessing the potential usefulness of targeting approaches for either autophages or inflammasomes as anti-cancer strategies. Expand
...
1
2
...

References

SHOWING 1-10 OF 64 REFERENCES
Translation Elongation Factor eEF1A2 is a Novel Anticancer Target for the Marine Natural Product Plitidepsin
TLDR
It is demonstrated that plitidepsin exerts its antitumor activity by targeting eEF1A2, one of the isoforms of the alpha subunit of the eukaryotic Elongation Factor 1, which is endowed with oncogenic properties, favoring tumor cell proliferation while inhibiting apoptosis. Expand
Eukaryotic Elongation Factor 1A Interacts with Sphingosine Kinase and Directly Enhances Its Catalytic Activity*
TLDR
This study has established a novel mechanism of regulation of both SK1 and SK2 that is mediated by their interaction with eEF1A, and shows that e EF1A is able to directly increase the activity of SK1and SK2 ∼3-fold in vitro. Expand
The eEF1A Proteins: At the Crossroads of Oncogenesis, Apoptosis, and Viral Infections
TLDR
It is indicated that eEF1A proteins play a critical role in numerous human diseases through enhancement of oncogenesis, blockade of apoptosis, and increased viral pathogenesis. Expand
Guanine nucleotides regulate sphingosine kinase 1 activation by eukaryotic elongation factor 1A and provide a mechanism for eEF1A-associated oncogenesis
TLDR
This study defines the mechanism regulating eEF1A-mediated SK1 activation, and establishes SK1 as being integral for PTI-1-induced oncogenesis, and shows that enhancing cellular e EF1A.GDP levels through expression of a guanine nucleotide dissociation inhibitor of eEF2A, translationally controlled tumour protein (TCTP), increased SK1 activity in cells. Expand
Mouse translation elongation factor eEF1A‐2 interacts with Prdx‐I to protect cells against apoptotic death induced by oxidative stress
TLDR
The results suggest that eEF1A‐2 interacts with Prdx‐I to functionally provide cells with extraordinary resistance to oxidative stress‐induced cell death. Expand
Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action
TLDR
A detailed picture is provided on how signaling downstream of PKR unfolds and what are the ultimate consequences of the antiproliferative and antiviral effects exerted by interferons. Expand
Eef1a2 Promotes Cell Growth, Inhibits Apoptosis and Activates JAK/STAT and AKT Signaling in Mouse Plasmacytomas
TLDR
EEF1A2 may play contribute to the induction or progression of some PCT and a small percentage of MM, and could also prove to be a useful new marker for a subset of MM and a possible target for therapy. Expand
Up-regulation of eEF1A2 promotes proliferation and inhibits apoptosis in prostate cancer.
TLDR
The data suggests that eEF1A2 plays an important role in prostate cancer development, especially in inhibiting apoptosis, and might serve as a potential therapeutic target in prostatecancer. Expand
The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas
Ovarian epithelial carcinomas (OECs) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and theExpand
Characterisation of Translation Elongation Factor eEF1B Subunit Expression in Mammalian Cells and Tissues and Co-Localisation with eEF1A2
TLDR
It is shown that eEF1B subunits are all widely expressed to varying degrees in different cell lines and tissues, and at different stages of development, and that ablation of any of the subunits in human cell lines has a small but significant impact on cell viability and cycling. Expand
...
1
2
3
4
5
...