Moonlighting Functions of Polypeptide Elongation Factor 1: From Actin Bundling to Zinc Finger Protein R1-Associated Nuclear Localization

Ejiri, Shin-ichiro

doi:10.1271/bbb.66.1

Cited by 190 publications

(174 citation statements)

References 123 publications

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“…It is surprising that eukaryotic translation elongation factor 1A (eEF1A) was identified as a putative membrane receptor mediating the antiadhesive effect of this exposed site. eEF1A is a key player of the cytoplasm in polypeptide chain elongation during protein translation (26,27). Although there have been no reports of the membrane localization of eEF1A, our results of immunofluorescence confocal microscopic and flow cytometric analyses and immunoprecipitation studies support the residence of eEF1A on the outer cell surfaces.…”

Section: Cell Adhesion To the Extracellular Matrix (Ecm)supporting

confidence: 69%

“…The canonical role of eEF1A in protein translation is associated with a cytoplasmic function (26,27). To ascertain whether eEF1A is indeed resident on the outer surface of the plasma membrane, we sought to verify the location of eEF1A on the plasma membrane by immunofluorescence confocal microscopy and flow cytometry using a monoclonal antibody recognizing human eEF1A and WI38VA13 cells, which highly express eEF1A.…”

Section: Proteolytic Exposure Of the Cryptic Antiadhesive Site Withinmentioning

confidence: 99%

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Eukaryotic Translation Elongation Factor 1A Induces Anoikis by Triggering Cell Detachment

Itagaki

Naito

Iwakiri

et al. 2012

Journal of Biological Chemistry

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Background: Fibronectin harbors a cryptic antiadhesive site that is able to inactivate ␤-1 integrins. Results: Spontaneous anoikis of nontransformed fibroblasts was caused by exposure of this antiadhesive site and its recognition by membrane-resident eEF1A. Conclusion: eEF1A functions as a membrane receptor triggering cell detachment, resulting in anoikis.Significance: The results demonstrate a new function of eEF1A that contributes to cell regulation, including anoikis.

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Section: Cell Adhesion To the Extracellular Matrix (Ecm)supporting

confidence: 69%

Section: Proteolytic Exposure Of the Cryptic Antiadhesive Site Withinmentioning

confidence: 99%

Eukaryotic Translation Elongation Factor 1A Induces Anoikis by Triggering Cell Detachment

Itagaki

Naito

Iwakiri

et al. 2012

Journal of Biological Chemistry

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“…First, EEF1A2 has been shown to be a potential oncogene; it is overexpressed in a proportion of ovarian tumors but is not expressed in normal ovary (51), and it is similarly overexpressed in two-thirds of breast tumors but not normal breast tissue (52,53). Phosphorylation has been determined to modify some of the activities of mammalian eEF1A, typically resulting in a stimulatory effect (32,54). We observed that among the two isoforms only the mRNA expression of eEF1A2 is slightly up-regulated upon insulin administration, whereas eEF1A1 remained stable.…”

Section: Fig 6 Mutation On Sermentioning

confidence: 83%

eEF1A Phosphorylation in the Nucleus of Insulin-stimulated C2C12 Myoblasts

Piazzi

Bavelloni

Faenza

et al. 2010

Molecular & Cellular Proteomics

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Recent data indicate that some PKC isoforms are translocated to the nucleus, in response to certain stimuli, where they play an important role in nuclear signaling events. To identify novel interacting proteins of conventional PKC (cPKC) at the nuclear level during myogenesis and to find new PKC isozyme-specific phosphosubstrates, we performed a proteomics analysis of immunoprecipitated nuclear samples from mouse myoblast C2C12 cells following insulin administration. Using a phospho(Ser)-PKC substrate antibody, specific interacting proteins were identified by LC-MS/MS spectrometry. A total of 16 proteins with the exact and complete motif recognized by the phospho-cPKC substrate antibody were identified; among these, particular interest was given to eukaryotic elongation factor 1␣ (eEF1A). Nuclear eEF1A was focalized in the nucleoli, and its expression was observed to increase following insulin treatment. Of the cPKC isoforms, only PKC␤I was demonstrated to be expressed in the nucleus of C2C12 myocytes and to coimmunoprecipitate with eEF1A. In-depth analysis using site-directed mutagenesis revealed that PKC␤I could phosphorylate Ser 53 of the eEF1A2 isoform and that the association between eEF1A2 and PKC␤I was dependent on the phosphorylation status of eEF1A2. Molecular & Cellular Proteomics 9:2719 -2728, 2010.

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“…eEF1A proteins have canonical roles in protein synthesis, transporting aminoacyl transfer RNAs to the ribosome during polypeptide elongation (Abbott and Proud, 2004). Many other 'moonlighting' roles for eEF1A have, however, been described, including cytoskeletal remodelling, enzyme regulation and apoptosis (Ejiri, 2002). Furthermore, substantial evidence now exists that deregulation of eEF1A can lead to cancer (Al-Maghrebi et al, 2005), although the molecular mechanisms whereby this occurs remain undefined.…”

Section: Introductionmentioning

confidence: 99%

Guanine nucleotides regulate sphingosine kinase 1 activation by eukaryotic elongation factor 1A and provide a mechanism for eEF1A-associated oncogenesis

2010

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Sphingosine kinase 1 (SK1) catalyses the formation of bioactive phospholipid sphingosine 1-phosphate (S1P). Elevated cellular SK1 activity and S1P levels enhance cell proliferation and survival, and are strongly implicated in tumourigenesis. Regulation of SK1 activity can occur through various mechanisms, including phosphorylation and protein-protein interactions. We have previously shown that eukaryotic elongation factor 1A (eEF1A) interacts with and directly activates SK1, but the mechanisms regulating this were undefined. Notably, eEF1A has GTPase activity and can exist in GTP-or GDP-bound forms, which are associated with distinct structural conformations of the protein. Here, we show that the guanine nucleotide-bound state of eEF1A regulates its ability to activate SK1, with eEF1A.GDP, but not eEF1A.GTP, enhancing SK1 activity in vitro. Furthermore, we show that enhancing cellular eEF1A. GDP levels through expression of a guanine nucleotide dissociation inhibitor of eEF1A, translationally controlled tumour protein (TCTP), increased SK1 activity in cells. We also examined a truncated isoform of eEF1A1, termed prostate tumour inducer-1 (PTI-1), which can induce neoplastic cell transformation through undefined mechanisms. PTI-1 lacks the G protein domain of eEF1A1 and is therefore unable to undergo the GTP-binding-induced conformational change. Notably, we found that PTI-1 can directly activate SK1 and that this seems to be essential for neoplastic transformation induced by PTI-1, as chemical SK1 inhibitors or overexpression of a dominant-negative SK1 blocked this process. Thus, this study defines the mechanism regulating eEF1A-mediated SK1 activation, and also establishes SK1 as being integral for PTI-1-induced oncogenesis.

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Moonlighting Functions of Polypeptide Elongation Factor 1: From Actin Bundling to Zinc Finger Protein R1-Associated Nuclear Localization

Cited by 190 publications

References 123 publications

Eukaryotic Translation Elongation Factor 1A Induces Anoikis by Triggering Cell Detachment

Eukaryotic Translation Elongation Factor 1A Induces Anoikis by Triggering Cell Detachment

eEF1A Phosphorylation in the Nucleus of Insulin-stimulated C2C12 Myoblasts

Guanine nucleotides regulate sphingosine kinase 1 activation by eukaryotic elongation factor 1A and provide a mechanism for eEF1A-associated oncogenesis

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