Role of eIF3a (eIF3 p170) in intestinal cell differentiation and its association with early development

Liu, Zhao‐Qian; Dong, Zizheng; Yang, Zhangping; Chen, Qun; Pan, Yi; Yang, Youyun; Cui, Ping; Zhang, Xin; Zhang, Jian-Ting

doi:10.1111/j.1432-0436.2007.00165.x

Cited by 49 publications

(51 citation statements)

References 37 publications

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“…It has been previously suggested that p170/eIF3A may not be an essential contributor in the function of the eIF3 complex during the initiation of mRNA translation (6). On the other hand, other studies have shown that p170/eIF3A participates in the control of translation for a subset of mRNAs (10,12,32). Our findings raise the possibility of a unique function of p170/eIF3A, playing an essential role in facilitating eIF4B-associated ATPase activity during the initiation of mRNA translation by IFNs.…”

Section: Discussionmentioning

confidence: 49%

Interferon-Dependent Engagement of Eukaryotic Initiation Factor 4B via S6 Kinase (S6K)- and Ribosomal Protein S6K-Mediated Signals

Kroczyńska

Kaur

Katsoulidis

et al. 2009

Molecular and Cellular Biology

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Although the roles of Jak-Stat pathways in type I and II interferon (IFN)-dependent transcriptional regulation are well established, the precise mechanisms of mRNA translation for IFN-sensitive genes remain to be defined. We examined the effects of IFNs on the phosphorylation/activation of eukaryotic translation initiation factor 4B (eIF4B). Our data show that eIF4B is phosphorylated on Ser422 during treatment of sensitive cells with alpha IFN (IFN-␣) or IFN-␥. Such phosphorylation is regulated, in a cell type-specific manner, by either the p70 S6 kinase (S6K) or the p90 ribosomal protein S6K (RSK) and results in enhanced interaction of the protein with eIF3A (p170/eIF3A) and increased associated ATPase activity. Our data also demonstrate that IFN-inducible eIF4B activity and IFN-stimulated gene 15 protein (ISG15) or IFN-␥-inducible chemokine CXCL-10 protein expression are diminished in S6k1/S6k2 double-knockout mouse embryonic fibroblasts. In addition, IFN-␣-inducible ISG15 protein expression is blocked by eIF4B or eIF3A knockdown, establishing a requirement for these proteins in mRNA translation/protein expression by IFNs. Importantly, the generation of IFN-dependent growth inhibitory effects on primitive leukemic progenitors is dependent on activation of the S6K/eIF4B or RSK/eIF4B pathway. Taken together, our findings establish critical roles for S6K and RSK in the induction of IFN-dependent biological effects and define a key regulatory role for eIF4B as a common mediator and integrator of IFN-generated signals from these kinases.Extensive work over the years has established that the control of initiation of mRNA translation occurs primarily at the step at which the 40S ribosomal subunit is recruited to mRNA, to be positioned at the initiation codon (15). Most eukaryotic mRNAs contain a 5Ј cap structure (m7GpppN) to which the cap-binding protein complex eukaryotic initiation factor 4F (eIF4F) is attached. eIF4F is composed of three subunits: eIF4E, the cap-binding subunit; eIF4A, a protein with RNA helicase activity that unwinds the mRNA 5Ј secondary structure; and eIF4G, a scaffolding protein that associates with other IFs (15,18,20,37,54). The unphosphorylated/activated form of the translational repressor 4E-BP1 (eIF4E-binding protein 1) competes with eIF4G for binding to eIF4E and blocks cap-dependent mRNA translation (37), while such 4E-BP1-eIF4E interactions are decreased when phosphorylation of 4E-BP1 occurs by the mammalian target of rapamycin (mTOR) kinase (15,18,20,37,54). Beyond phosphorylation of 4E-BP1, mTOR regulates activation of the p70 S6 kinase (S6K), which in turn phosphorylates several substrates, including the S6 ribosomal protein (rpS6), eIF4B, and the tumor suppressor PDCD4 (13,18,20,54).Although much is known about the roles of mTOR-generated signals in the control of mRNA translation for cytokines and growth factors, the roles of various mTOR effectors in the initiation of mRNA translation in response to interferons (IFNs) remain to be precisely defined. Type I (␣, ␤, ε, , and ) and I...

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Section: Discussionmentioning

confidence: 49%

Interferon-Dependent Engagement of Eukaryotic Initiation Factor 4B via S6 Kinase (S6K)- and Ribosomal Protein S6K-Mediated Signals

Kroczyńska

Kaur

Katsoulidis

et al. 2009

Molecular and Cellular Biology

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“…Another subunit, eIF3a, involved in cell proliferation and tissue development has also been found highly overexpressed in several human and murine cancer tissues [21,22]. In fact, many studies have reported the role of eIF3a as an early differentiation marker in human mammary carcinoma cells, although the role of this subunit in oncogenesis is still unclear.…”

Section: Ch-senps Exposure Affects the Expression Of The Eif3 Proteinmentioning

confidence: 99%

Effect of Chitosan-Stabilized Selenium Nanoparticles on Cell Cycle Arrest and Invasiveness in Hepatocarcinoma Cells Revealed by Quantitative Proteomics

Heras¹

2014

J Nanomed Nanotechnol

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Selenium nanoparticles have been recently proposed as a potential chemotherapeutic agent due to its low toxicity and its ability to arrest the cell cycle of cancer cells. However, the biochemical mechanisms associated to this effect have not yet been uncovered. We evaluate here the potential of chitosan-stabilized selenium nanoparticles to induce cell cycle arrest and to inhibit in-vitro invasiveness in HepG2 cells. In addition, we use a quantitative proteomic approach to identify potential protein targets involved in the mechanisms associated to selenium nanoparticles exposure. Our data suggest that the induction of the cell cycle arrest at the S phase is mediated by de-regulation of the eIF3 protein complex. We found additional de-regulated proteins upon selenium nanoparticles exposure that could also be involved in the overall inhibition of cell proliferation. These findings not only support the potential of chitosan-stabilized selenium nanoparticles as anti-cancer therapy but also provide a deeper insight into the mechanisms associated to their chemotherapeutic effects.

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“…In addition to this capdependent translational process, eIF3 also plays an important role in cap independent translation regulation by binding to the putative internal ribosome entry site (IRES) element (18). eIF3a, the largest subunit of eIF3 complex, has been shown to play a role in regulating synthesis of proteins including a-tubulin, ribonucleotide reductase M2, and p27 (19,20) as well as in cell proliferation (19), cell cycle control (21), and cell differentiation (22). Overexpression of eIF3a has been found in many cancers such as cancers of lung (23), breast (23), cervix (24), stomach (25), and esophagus (26).…”

Section: Introductionmentioning

confidence: 99%

Effect of eIF3a on Response of Lung Cancer Patients to Platinum-Based Chemotherapy by Regulating DNA Repair

Yin

Shen

Dong

et al. 2011

Clinical Cancer Research

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Purpose: The purpose of this study is to test the hypothesis that eIF3a may regulate the expression of DNA repair proteins which, in turn, affects response of lung cancer patients to treatments by DNAdamaging anticancer drugs.Experimental Design: Immunohistochemistry was used to determine the expression of eIF3a in 211 human lung cancer tissues followed by association analysis of eIF3a expression with patient's response to platinum-based chemotherapy. Ectopic overexpression and RNA interference knockdown of eIF3a were carried out in NIH3T3 and H1299 cell lines, respectively, to determine the effect of altered eIF3a expression on cellular response to cisplatin, doxorubicine, etoposide (VP-16), vincristine, and vinblastine by using MTT assay. The DNA repair capacity of these cells was evaluated by using host-cell reactivation assay. Real-time reverse transcriptase PCR and Western Blot analyses were carried out to determine the effect of eIF3a on the DNA repair genes by using cells with altered eIF3a expression.Results: eIF3a expression associates with response of lung cancer patients to platinum-based chemotherapy. eIF3a knockdown or overexpression, respectively, increased and decreased the cellular resistance to cisplatin and anthrocycline anticancer drugs, DNA repair activity, and expression of DNA repair proteins.Conclusions: eIF3a plays an important role in regulating the expression of DNA repair proteins which, in turn, contributes to cellular response to DNA-damaging anticancer drugs and patients' response to platinum-based chemotherapy. Clin Cancer Res; 17(13); 4 -9. Ó2011 AACR.

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Role of eIF3a (eIF3 p170) in intestinal cell differentiation and its association with early development

Cited by 49 publications

References 37 publications

Interferon-Dependent Engagement of Eukaryotic Initiation Factor 4B via S6 Kinase (S6K)- and Ribosomal Protein S6K-Mediated Signals

Interferon-Dependent Engagement of Eukaryotic Initiation Factor 4B via S6 Kinase (S6K)- and Ribosomal Protein S6K-Mediated Signals

Effect of Chitosan-Stabilized Selenium Nanoparticles on Cell Cycle Arrest and Invasiveness in Hepatocarcinoma Cells Revealed by Quantitative Proteomics

Effect of eIF3a on Response of Lung Cancer Patients to Platinum-Based Chemotherapy by Regulating DNA Repair

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