Induced gene expression of the hypusine-containing protein eukaryotic initiation factor 5A in activated human T lymphocytes.

Bevec, Dorian; Klier, Hannelore; Holter, Wolfgang; Tschachler, Erwin; Valent, Peter; Lottspeich, Friedrich; Baumruker, Thomas; Hauber, Joachim

doi:10.1073/pnas.91.23.10829

Cited by 37 publications

(32 citation statements)

References 34 publications

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“…In yeast expression, eIF5A has been reported to correlate with cell proliferation (7). Further, eIF5A expression was induced in activated human T lymphocytes (10). This paradox could be reconciled by viewing the mechanisms of eIF5A not as isolated circuits, but as part of a coordinated process, which targets key nodes of cell signal networks for cell growth or apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the factor interacts with the general nuclear export receptor CRM1 during their transportation from the nucleus to the cytoplasm (9). The eIF5A protein expression was normally very low but inducible with T lymphocyte-specific stimuli in human peripheral blood mononuclear cells of healthy individuals, and a significant up-regulation of eIF5A mRNA was found in the peripheral blood mononuclear cells of human immunodeficiency virus type 1-infected patients (10). The eIF5A expression is also significantly increased during dendritic cell maturation, and hypusine formation appears to be essential for this process (11).…”

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confidence: 88%

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A Novel eIF5A Complex Functions As a Regulator of p53 and p53-dependent Apoptosis

Jin

et al. 2004

Journal of Biological Chemistry

113

105

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Although eukaryotic translation initiation factor 5A (eIF5A) was originally designated as an "initiation factor," recent data have shown it to be also involved in apoptosis. However, the actual function of eIF5A in apoptosis is still unknown. In this study, we performed yeast two-hybrid screens to identify eIF5A-interacting proteins to help us understand the mechanisms of eIF5A. Our results demonstrated that eIF5A and syntenin could engage in a specific interaction both in vitro and in vivo and functioned collaboratively to regulate p53 activity. Our findings, for the first time, revealed a new biological activity for eIF5A as the regulator of p53. Overexpression of eIF5A or its EFP domain resulted in up-regulation of p53, and silencing eIF5A by small interfering RNA reduced the p53 protein level. Further analysis by reverse transcription PCR showed eIF5A-activated p53 transcription. The effect of eIF5A on p53 transcriptional activity was further demonstrated by the increasing expressions of p21 and Bax, well known target genes of p53. In contrast, a point mutant of eIF5A, hypusination being abolished, was revealed to be functionally defective in p53 up-regulation. Overexpression of eIF5A led to a p53-dependent apoptosis or sensitized cells to induction of apoptosis by chemotherapeutic agents. However, when eIF5A interacted with its novel partner, syntenin, the eIF5A-induced increase in p53 protein level was significantly inhibited. Therefore, eIF5A seems to be a previously unrecognized regulator of p53 that may define a new pathway for p53-dependent apoptosis, and syntenin might regulate p53 by balancing the regulation of eIF5A signaling to p53 for apoptosis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 88%

A Novel eIF5A Complex Functions As a Regulator of p53 and p53-dependent Apoptosis

Jin

et al. 2004

Journal of Biological Chemistry

113

105

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“…It has been reported that, in mammalian cells, eIF-5A is present both in the cytoplasm and nucleus [3]. The reason that eIF-5A is named as an initiation factor comes from earlier observations that it can be isolated from the ribosome-bound fraction and is considered to be involved in the first step peptide bond formation in translation [4].…”

Section: Introductionmentioning

confidence: 99%

Crystallization and preliminary crystallographic analysis of human serine dehydratase

Sun

Dong

et al. 2003

Acta Crystallogr D Biol Cryst

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Eukaryotic translation initiation factor 5A (eIF-5A) is universally found in all eukaryotic cells. It is the only protein in nature known to contain the unusual amino acid hypusine, a post-translationally modified lysine. Recombinant human eIF-5A was crystallized by the hanging-drop vapor diffusion method. Crystals were grown at 291K using (NH 4 ) 2 SO 4 as precipitant. Diffraction data were obtained to a resolution of 2.7Å from a single frozen crystal belonging to space group C2, with unit-cell parameters a=147.1Å, b=60.4Å, c=76.4Å, β=92.4°. There are more than three molecules per asymmetric unit.

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“…In relation to the example mentioned above, an appropriate relation between the increase of eIF5A mRNA level and its protein in stimulated lymphocytes was found (4) . However, this relation is not found in some transcripts, because the mRNAs can be differentially recruited to translation process.…”

Section: Transcriptome Analysis Limitationsmentioning

confidence: 99%

“…For instance, unstimulated T lymphocytes present a low rate of eIF5A gene transcriptional activity. However, stimulation by specific mediators leads to an increase in the rate of eIF5A transcription (4) . In this context, the differential transcriptome analysis in relation to coding mRNAs of protein isoforms has to be carefully interpreted, because some systems are not able to make a distinction due to their high identity.…”

Section: Eif5a and The Mrnas Metabolismmentioning

confidence: 99%

Envolvimento do fator de início de tradução de eucariotos 5A (elF5A) na diferenciação de células-tronco da musculatura esquelética

Luchessi¹

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Taking the eukaryotic translation initiation factor 5A (eIF5A) as model, some aspects of different points of gene expression control and transcriptome studies are discussed. A parallel with proteomic studies is presented, as well as the optimization of the transcriptome analysis using polysome profile assay. The polysome profile assay application reveals the translational control of mRNAs not identified by traditional differential analysis of transcriptomes, which is widely employed to study diseases, such as tumors.Keywords: Polysome profile; Transcriptome; Translational control; Post-transcriptional; eIF5A protein; eIF-5A; Proteome RESUMOUtilizando o fator de início de tradução de eucariotos 5A (eIF5A) como modelo, alguns aspectos dos diferentes pontos de controle da expressão gênica e estudo de transcriptomas são discutidos. Um paralelo da aplicação de estudos proteômicos é abordado e a otimização da análise de transcriptomas utilizando o ensaio de perfil polissomal é evidenciada. O uso do ensaio de perfil polissomal revela o controle traducional de mRNAs não identificados pela análise diferencial tradicional de transcriptomas amplamente empregada no estudo de doenças como tumores.Descritores: Perfil polissomal; Transcriptoma; Controle traducional; Pós-transcricional; Proteína eIF5A; eIF-5A; Proteoma THE EUKARYOTIC TRANSLATION INITIATION FACTOR 5AThe eukaryotic translation initiation factor 5A (eIF5A) is the only protein known to contain the amino acid residue hypusine, produced by a post-translational modification called hypusination(1) (figure 1). This modification is initiated by the transfer of a 4-aminobutyl moiety from polyamine spermidine to an e-amino group of a specific lysine residue of the eIF5A precursor; a reaction catalyzed by deoxyhypusine synthase (DHS). Afterwards, the hypusine residue is formed by hydroxylation of the deoxyhypusine residue; a reaction catalyzed by deoxyhypusine hydroxylase (DHH). The protein eIF5A is highly conserved in archaebacteria and eukaryotic cells (1) . Some studies revealed a strong association of eIF5A with cell proliferation. In fact, any interference in hypusination process promotes cell proliferation inhibition (2) . However, the precise function of eIF5A is not understood but it has been proposed to be associated with mRNA metabolism. eIF5A AND THE mRNAS METABOLISMThe metabolism of mRNAs is an important target to control gene expression. This control can be carry out in several steps, such as mRNA synthesis, posttranscriptional processing, nuclear pore transport, recruitment to translation and degradation (figure 2). The comparative transcriptome analysis reveals differential levels of mRNAs controlled by its metabolism.

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Induced gene expression of the hypusine-containing protein eukaryotic initiation factor 5A in activated human T lymphocytes.

Cited by 37 publications

References 34 publications

A Novel eIF5A Complex Functions As a Regulator of p53 and p53-dependent Apoptosis

A Novel eIF5A Complex Functions As a Regulator of p53 and p53-dependent Apoptosis

Crystallization and preliminary crystallographic analysis of human serine dehydratase

Envolvimento do fator de início de tradução de eucariotos 5A (elF5A) na diferenciação de células-tronco da musculatura esquelética

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