Truncated initiation factor eIF4G lacking an eIF4E binding site can support capped mRNA translation

Ali, Iraj K.; McKendrick, Linda; Morley, Simon; Jackson, Richard J.

doi:10.1093/emboj/20.15.4233

Cited by 77 publications

(73 citation statements)

References 34 publications

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“…Along these lines, we note that eIF4G can function in stimulating mRNA translation independent of eIF4E. Truncated mutants of eIF4G that lack the eIF4E-binding site have been shown to stimulate translation of uncapped mRNAs in rabbit reticulocyte lysate (RRL) (23), restored translation of capped mRNAs in eIF4F-depleted RRL (24), and in vivo can stimulate initiation of translation (25). In reconstituted systems, eIF4G (lacking the eIF4E binding site) and eIF4A can efficiently load 48S complexes on capped and uncapped ß-globin mRNA (26).…”

Section: Discussionmentioning

confidence: 97%

Reversing chemoresistance by small molecule inhibition of the translation initiation complex eIF4F

Cencic¹,

Hall

Robert³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

154

185

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The authors note that, due to a printer's error, on page 3787, right column, first paragraph, lines 8-20, "Although significant evidence supports a primary role for the 5-HT transporter in the reinforcing properties of psychostimulants (35-37), SERT blockade also appears to contribute to reinforcement (38-40).Indeed, SERT appears to be primarily responsible for the sustained reinforcing properties of cocaine in the 5-HT transporter-KO mouse (22,23,(39)(40)(41). The significant compensatory alterations evident in 5-HT transporter-KO mice encouraged Chen and colleagues (42, 43) to develop a mouse bearing knock-in mutations in 5-HT transporter that, in vitro, reduced cocaine potency. Studies with these mice have yielded convincing evidence that 5-HT transporter is a key determinant of many synaptic and behavioral actions of cocaine" should instead appear as "Although significant evidence supports a primary role for the DA transporter in the reinforcing properties of psychostimulants (35-37), SERT blockade also appears to contribute to reinforcement (38-40). Indeed, SERT appears to be primarily responsible for the sustained reinforcing properties of cocaine in the DA transporter-KO mouse (22,23,(39)(40)(41). The significant compensatory alterations evident in DA transporter-KO mice encouraged Chen and colleagues (42, 43) to develop a mouse bearing knock-in mutations in the DA transporter that, in vitro, reduced cocaine potency. Studies with these mice have yielded convincing evidence that the DA transporter is a key determinant of many synaptic and behavioral actions of cocaine." www.pnas.org/cgi

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Section: Discussionmentioning

confidence: 97%

Reversing chemoresistance by small molecule inhibition of the translation initiation complex eIF4F

Cencic¹,

Hall

Robert³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

154

185

View full text Add to dashboard Cite

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“…This factor has been shown to facilitate cap-dependent translation even if it lacks eIF4E-binding site. 31 EIF2A is a regulatory subunit of eIF-2, the phosphorylation of which leads to inactivation of the translation initiation complex. Selective pressure during tumor progression may lead to elimination or to a markedly decreased expression of EIF2A preventing the decrease of eIF-2 activity upon EIF2A phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Frequent overexpression of the genes FXR1, CLAPM1 and EIF4G located on amplicon 3q26‐27 in squamous cell carcinoma of the lung

Comtesse

Keller

Diesinger

et al. 2007

Intl Journal of Cancer

100

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Previously, we reported gene amplification at chromosome 3q26-27 in more than one third of squamous cell carcinomas of the lung. Frequent amplification of eukaryotic translation initiation factor 4G on 3q27.1 indicated a possible role of this amplification in translation initiation. The analysis of 61 squamous cell lung carcinomas shows that the percentage of carcinomas with a 3q27.1 amplification increases in higher malignant tumors. Non-invasive (T1) and minimal-invasive (T2) tumor stages showed similar percentages of amplified and non-amplified tumors, whereas locallyinvasive (T3) tumors revealed a statistically significant (p < 0.05) increased percentage of amplified tumors. Microarrays were used to analyze the expression pattern of genes mapping in the amplified domain and its flanking regions (3q25-28) as well as the expression of genes directly or indirectly associated with translation initiation in squamous cell carcinoma, large cell carcinoma, adenocarcinoma and small cell carcinoma. Three genes, namely FXR1, CLAPM1 and EIF4G, are most frequently overexpressed in the center of the amplified domain in squamous cell carcinomas. The eukaryotic translation initiation factors 4A1, 2B and 4B as well as the poly(A)-binding protein PABPC1 where found to be overexpressed in all lung cancer entities. We found, however, no overexpression of eIF4E. Our results contribute to the understanding of the frequent amplification processes in squamous cell carcinomas of the lung and to the understanding of the translation initiation that appears not to require eIF4E in lung carcinogenesis. ' 2007 Wiley-Liss, Inc.

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“…During apoptosis, eIF4G is cleaved by caspase-3 and PABP is cleaved by an as yet unidentified protease (Marissen and Lloyd 1998;M arissen et al 2004). Interestingly, fragments of eIF4G are knownt om ediate both IRES-mediated translation of both transcriptionf actor c-myc and proapoptotic mRNAsApaf-1 and DAP5 and low levels of capdependent initiation (Ali et al 2001;Nevins et al 2003;Hundsdoerfer et al 2005). It is possible that fragments of eIF4Ga nd/orP ABP derived by viral protease cleavage are not competent to elicit initiatione vents within the cytosol buta re able to specifically stimulate ER-localizedt ranslation.…”

Section: Discussionmentioning

confidence: 99%

mRNA translation is compartmentalized to the endoplasmic reticulum following physiological inhibition of cap-dependent translation

Lerner¹,

Nicchitta²

2006

RNA

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Eukaryotic cells utilize ac ycle of ribosome trafficking on the endoplasmic reticulum (ER) to partition mRNAs between the cytosol and ER compartments. In this process, ribosomes engaged in the synthesis of signal sequence-bearing proteins are trafficked to the endoplasmic reticulum via the signal-recognition particle pathway and are released from the ER upon translation termination. Though the processes governing ribosome trafficking to the ER are well understood, little is known regarding the complementary ribosome release process. In this study, Coxsackie Bvirus (CBV) infection was used to inactivate the initiation stage of protein synthesis, thereby limiting translation to the elongation and termination stages. Ribosome partitioning between the cytosol and ER compartments was examined to determine the role of termination in ribosome release from the ER. CBV infection resulted in efficient cleavage of eIF4G and PABP, coincident with polyribosome breakdown in the cytosol and ER compartments. Termination resulted in the continued association of ribosomes with the ER compartment, rather than the expected process of ribosome release. Analyses of ribosome/mRNA loading patterns in the cytosol and ER revealed that CBV infection was accompanied by as uppression of mRNA translation in the cytosol and the sustained, although reduced, translation in the ER compartment. Direct biosynthetic labeling experiments demonstrated that protein synthesis on the ER was enhanced relative to the cytosol following CBV infection. In total, these data demonstrate that ribosome and mRNA release from the ER is regulated independent of translation termination and identify the ER as ap rivileged site for protein synthesis.

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Truncated initiation factor eIF4G lacking an eIF4E binding site can support capped mRNA translation

Cited by 77 publications

References 34 publications

Reversing chemoresistance by small molecule inhibition of the translation initiation complex eIF4F

Reversing chemoresistance by small molecule inhibition of the translation initiation complex eIF4F

Frequent overexpression of the genes FXR1, CLAPM1 and EIF4G located on amplicon 3q26‐27 in squamous cell carcinoma of the lung

mRNA translation is compartmentalized to the endoplasmic reticulum following physiological inhibition of cap-dependent translation

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