Decreased expression of eukaryotic initiation factor 3f deregulates translation and apoptosis in tumor cells

Shi, Jiaqi; Kahle, Amber C.; Hershey, John W.B.; Honchak, Barbara M.; Warneke, James; Leong, Stanley P. L.; Nelson, Mark A.

doi:10.1038/sj.onc.1209495

Cited by 104 publications

(176 citation statements)

References 32 publications

(44 reference statements)

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“…Similar results have been obtained for other eIF3 subunits (Shi et al, 2006). Thus, it is plausible that fine-tuning of the cellular level of eIF3e has a regulatory role.…”

Section: Discussionsupporting

confidence: 75%

Arabidopsis eIF3e is regulated by the COP9 signalosome and has an impact on development and protein translation

et al. 2007

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SummaryThe roles of individual eukaryotic translation initiation factor 3 (eIF3) subunits are largely unclear, although some are essential, while others are thought to have regulatory roles. The 'e' subunit, also known as Int-6/Int6, is a candidate for a regulatory subunit as it is not essential for translation initiation in yeasts. eIF3e associates with the COP9 signalosome, and localizes to the nucleus in certain tissues. To further elucidate the roles of eIF3e, we have taken a genetic approach using Arabidopsis as a model system. Overexpression of eIF3e results in defects similar to mutations in the COP9 signalosome. eIF3e protein, but not transcript, over accumulates in csn mutants, and eIF3e is degraded in a proteasome-dependent fashion. In vitro and in vivo assays suggest that excess eIF3e inhibits translation. We conclude that the COP9 signalosome maintains a precise regulation of eIF3e levels, which is necessary for normal development in Arabidopsis.

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“…Similar results have been obtained for other eIF3 subunits (Shi et al, 2006). Thus, it is plausible that fine-tuning of the cellular level of eIF3e has a regulatory role.…”

Section: Discussionsupporting

confidence: 75%

Arabidopsis eIF3e is regulated by the COP9 signalosome and has an impact on development and protein translation

et al. 2007

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“…Expression in our positive control tissue eliminated the possibility of poor antibody efficacy or influence of other preanalytic factors. Nevertheless, there is immunohistochemical evidence that eIF3 expression is decreased in pancreatic cancer (24,41). Further evidence from cancer profiling arrays shows general downregulation of eIF3 in human tumors (24), which may explain its lack of expression.…”

Section: Discussionmentioning

confidence: 99%

“…The role of initiation factors in the progression to a malignant phenotype is reported in many cancers, including, breast, head and neck, liver, prostate, bladder, gastric, colon, ovarian, glioma, lymphoma, non-small cell lung carcinoma, cervical, small intestine, and melanoma (20,(23)(24)(25). This has highlighted eIFs, notably eIF4E, as indicative of poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Humphries

Rajan

Droop

et al. 2017

Clinical Cancer Research

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Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar.Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n ¼ 477, training; n ¼ 220, validation set) and quantified in pre-and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor.Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P ¼ 0.013; HR ¼ 1.77, 1.12-2.8 and P ¼ 0.035; HR ¼ 1.68, 1.03-2.74, respectively), or when coexpressed (P ¼ 0.01; HR ¼ 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [eIF4E P ¼ 0.016; HR ¼ 2.38 (1.18-4.8), eIF5 P ¼ 0.022; HR ¼ 2.55 (1.14-5.7); coexpression P ¼ 0.001; HR ¼ 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival.Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required.

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“…It is a negative regulator of translation and cell growth, and it is also involved in apoptosis. eIF3f might play important roles in the regulation of eIF3 activity for translation of specific mRNAs (Shi et al ., 2006).…”

Section: Resultsmentioning

confidence: 99%

Longevity determined by developmental arrest genes in Caenorhabditis elegans

et al. 2007

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SummaryThe antagonistic pleiotropy theory of aging proposes that aging takes place because natural selection favors genes that confer benefit early on life at the cost of deterioration later in life. This theory predicts that genes that impact development would play a key role in shaping adult lifespan. To better understand the link between development and adult lifespan, we examined the genes previously known to be essential for development. From a pool of 57 genes that cause developmental arrest after inhibition using RNA interference, we have identified 24 genes that extend lifespan in Caenorhabditis elegans when inactivated during adulthood. Many of these genes are involved in regulation of mRNA translation and mitochondrial functions. Genetic epistasis experiments indicate that the mechanisms of lifespan extension by inactivating the identified genes may be different from those of the insulin/insulin-like growth factor 1 (IGF-1) and dietary restriction pathways. Inhibition of many of these genes also results in increased stress resistance and decreased fecundity, suggesting that they may mediate the trade-offs between somatic maintenance and reproduction. We have isolated novel lifespanextension genes, which may help understand the intrinsic link between organism development and adult lifespan.

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Decreased expression of eukaryotic initiation factor 3f deregulates translation and apoptosis in tumor cells

Cited by 104 publications

References 32 publications

Arabidopsis eIF3e is regulated by the COP9 signalosome and has an impact on development and protein translation

Arabidopsis eIF3e is regulated by the COP9 signalosome and has an impact on development and protein translation

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Longevity determined by developmental arrest genes in Caenorhabditis elegans

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