Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

EIF4B (eukaryotic translation initiation factor 4B)

Written2014-04Thomas Sbarrato, Emilie Horvilleur, Tuija Pöyry, Anne E Willis
Medical Research Council Toxicology Unit, Hodgkin Building, PO Box 138, Lancaster Rd, Leicester, LE1 9HN, UK

Abstract Review on eIF4B, with data on DNA/RNA, on the protein encoded and where the gene is implicated.

(Note : for Links provided by Atlas : click)

Identity

Other aliasEIF-4B
PRO1843
HGNC (Hugo) EIF4B
LocusID (NCBI) 1975
Atlas_Id 53571
Location 12q13.13  [Link to chromosome band 12q13]
Location_base_pair Starts at 53006258 and ends at 53042215 bp from pter ( according to hg19-Feb_2009)  [Mapping EIF4B.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
EIF4B (12q13.13) / C3orf58 (3q24)EIF4B (12q13.13) / TNNC1 (3p21.1)EIF4B (12q13.13) / UPP1 (7p12.3)
FYTTD1 (3q29) / EIF4B (12q13.13)ZNF384 (12p13.31) / EIF4B (12q13.13)

DNA/RNA

 
  Figure 1: Schematic representation of eIF4B gene, which is composed of 15 exons shown in blue.
Description The eIF4B gene codes for EIF4B protein. eIF4B gene is 69.15 kb in length and is composed of 15 exons (Figure 1).
Transcription eIF4B mRNA is ubiquitously expressed, however, regulation of eIF4B transcription has not been studied in detail.

Protein

 
  Figure 2: Schematic representation of eIF4B protein. The numbers refer to amino acids flanking the functional domains. Ser406 and Ser422 that can be phosphorylated by several kinases are indicated.
Description eIF4B is a 79kDA protein composed of 611 residues. Many sites of phosphorylation have been found for this protein using proteomics tools, including 29 Ser, 13 Thr and 1 Tyr (Prasad et al., 2009). Among them, two have been validated by further studies. The best studied phosphorylation site is Ser422 by p70/S6kinase in response to mTOR pathway (Holz et al., 2005). Ser422 can also be phosphorylated by p90 (RSK) and PKB (Shahbazian et al., 2006; van Gorp et al., 2009). Ser406 phosphorylation is cell cycle dependent and under control of mTOR and MAP kinase pathways (van Gorp et al., 2009). Ser406 is a target of Pim kinases (Yang et al., 2013). Finally, eIF4B is cleaved by caspase 3 after Asp45 during apoptosis (Bushell et al., 2001) (Figure 2).
Expression The protein is reported to be expressed in most tissues, excluding liver, smooth muscle or soft tissues (Uhlen et al., 2010). Given the crucial role played by this protein in the cell, it is expected to be expressed ubiquitously albeit probably to different levels throughout different tissues.
Localisation eIF4B has a cytoplasmic localisation.
 
  Figure 3: Initiation of translation.
Function eIF4B is an RNA binding protein involved in the regulation of the initiation stage of protein synthesis. This protein is critical for the recruitment of the mRNA to the ribosome. It helps unwind secondary structures in the mRNA to allow ribosome scanning, via enhancing both ATPase and helicase activities of eIF4A.
Translation of an mRNA initiates with the binding of eukaryotic initiation factor complex eIF4F comprised of eIF4E, eIF4G and eIF4A (Pestova and Kolupaeva, 2002) (Figure 3):
- eIF4E interacts directly with the cap of the mRNA and helps recruit the machinery to the 5'end of the mRNA.
- eIF4G protein provides a scaffold, bridging interactions between eIF4A, eIF4E, eIF3, PABP and RNA.
- Secondary structures in the mRNA that can be detrimental to the binding/scanning of the ribosome are unwound by the helicase eIF4A and its cofactors eIF4B and eIF4H (Grifo et al., 1983; Lawson et al., 1989; Rozen et al., 1990).
The binding of this eIF4F complex allows for the circularisation of the mRNA and the subsequent recruitment of the 43S pre-initiation complex (PIC) composed of the small ribosomal subunit (40S), the ternary complex (eIF2/met-tRNA/GTP) and several initiation factors (eIF1, eIF1A, eIF3 and eIF5) (Deo et al., 1999; Imataka et al., 1998; Lamphear et al., 1995; Wells et al., 1998). This complex will then scan the untranslated region (UTR) of the mRNA until a start codon is recognised (Kozak, 2002).
eIF4B acts at different levels to stimulate translation initiation: 1) by enhancing the ATPase and helicase activities of eIF4A and 2) by facilitating the recruitment of the 43S PIC.

1) Role of eIF4B in the stimulation of eIF4A
Although the precise mechanisms of action of eIF4B on the enhanced helicase activity of eIF4F are not fully understood, knockdown/aberrant expression of eIF4B in mammalian cells led to the reduction/stimulation in translation of mRNAs containing highly structured 5'UTRs (Horvilleur et al., 2013; Shahbazian et al., 2010). Additionally, the ATPase and helicase activity of free eIF4A was shown to be significantly slower than the rates of translation initiation or the rates of scanning of the PIC (Grifo et al., 1984; Pause et al., 1994; Richter-Cook et al., 1998).
Consequently, one can envisage that eIF4B can help in the substrate (ATP and RNA) recognition by eIF4A. As such, eIF4B can modulate the affinity for ATP and RNA by inducing conformational changes in eIF4A (Bi et al., 2000; Marintchev et al., 2009; Methot et al., 1994; Nielsen et al., 2011; Rogers Jr. et al., 2001; Rozovsky et al., 2008). Additionally, eIF4B can enhance the efficiency of this process by coupling the ATP hydrolysis to duplex unwinding to avoid redundant, energy-consuming events (Ozes et al., 2011). In a manner similar to other single-stranded DNA binding proteins that associate with helicases, one possible mode of action for eIF4B is to stabilize newly unwound single-stranded RNA. In support of this, a direct interaction between eIF4A and eIF4B in the presence of RNA and an ATP analog have been established via the C terminal region of eIF4B (Nielsen et al., 2011; Rozovsky et al., 2008).

2) Role of eIF4B in the recruitment of 43S PIC to mRNAs
Through its various domains, eIF4B is now known to promote the association of the various players in the recruitment of the 43S PIC to the mRNA. The C terminal RNA binding domain of eIF4B enables its binding to mRNA whereas the RRM motif triggers interaction with the rRNA from the 43S PIC (Methot et al., 1996a; Naranda et al., 1994). The latter is thought to anchor the helicase eIF4A to the scanning ribosome (Methot et al., 1996a). Importantly, mammalian eIF4B dimerises and binds to eIF3a via its DRYG repeats, thus providing a main link between the eIF4F-loaded mRNA and the 43S PIC (Methot et al., 1996b).
These results provide evidence that eIF4B participates in recruitment and assembly of the PIC on mRNAs. Critically, recent findings have now shown that interactions involving eIF4B via its different domains are essential for the effective assembly and efficient scanning of the 43S PIC. Yeast eIF4B together with eIF4F and eIF3 decreased the dependency on high concentrations of eIF4A for the rapid assembly and recruitment of the 43S PIC on endogenous short leader mRNAs (Mitchell et al., 2010; Walker et al., 2013), thus eIF4B can mediate an enhancing effect on the PIC recruitment to an mRNA.

The spatial positioning of eIF4B on the scanning ribosome is poorly understood. The helicase complex eIF4A/eIF4B could be located near the mRNA exit channel (i.e. 5'/behind the scanning PIC) or alternatively at the mRNA entry channel (i.e. 3'/in front of the scanning PIC) (Figure 4). To support the former hypothesis, a Brownian ratchet model was proposed in which eIF4F is located near the exit channel of the PIC (Spirin, 2009). In this model, eIF4A-unwound and eIF4B-captured single-stranded RNA would be scanned by diffusion by the PIC. Contradictory, new evidence have shown that yeast eIF4B mapped to the head of the PIC near the entry channel (Walker et al., 2013). In such a case, the eIF4F complex would be recruited to the cap and would be located at the forefront of the PIC, thus allowing efficient unwinding and scanning (Marintchev et al., 2009). New experimental approaches, including structures of the human ribosome associated with factors, should be able to shed some light on the matter in the future.

 
  Figure 4: Two possible models for eIF4B position in the initiation complex during scanning of 5'UTR.
Homology eIF4B is one of the least conserved initiation factors in terms of sequence homology (Cheng and Gallie, 2006), however, its function is conserved and eIF4B homologues can be found across all eukaryotic species. In addition to the human eIF4B, one of the most studied eIF4B homologs is the yeast protein, TIF3 (Altmann et al., 1993). eIF4H is a 23kDa paralog of eIF4B showing homology to the RRM RNA binding domain. eIF4H stimulates eIF4A helicase activity in a similar way to eIF4B.

Implicated in

Note
  
Entity General role in cancer
Note eIF4B expression and phosphorylation are de-regulated in many cancers. In particular, Ser422 phosphorylation is at the crossroad of two major pathways in oncogenesis: MAP kinases and AKT/mTOR pathway (Shahbazian et al., 2006) (Figure 5). In response to these signalling pathways, eIF4B activates both global translation, driving faster proliferation, and overexpression of specific oncoproteins such as MYC or BCL2 (Shahbazian et al., 2010). Activation of eIF4B and subsequent c-MYC induction is involved in arsenic-induced transformation in mouse epithelial cells (Zhang et al., 2011). Moreover, binding of 14-3-3 sigma tumour suppressor to eIF4B in late mitosis regulates translation indicating direct involvement of eIF4B in regulation of cell cycle (Wilker et al., 2007). Finally, eIF4B is cleaved by a caspase dependent mechanism upon activation of tumour necrosis factor pathway, suggesting a role in preventing apoptosis (Jeffrey et al., 2002).
 
Figure 5: mTOR and MEK/ERK/MAP kinase pathways converge on eIF4B.
  
  
Entity Nasopharyngeal carcinoma (NPC)
Note Although not mutated, p53 is known to be up-regulated in NPC. In a proteomic study, eIF4B was shown to be down-regulated following p53 knockdown in a NPC cell line (Sun et al., 2007).
  
  
Entity T-cell lymphoblastic leukemia/lymphoma
Note eIF4B mRNA was found to be up-regulated in a genome wide study comparing mouse model of thymic tumours (lymphoblastic leukaemia precursor) to untransformed thymus (Lin and Aplan, 2007).
  
  
Entity Gastric cancer
Note A microarray study found eIF4B mRNA to be up-regulated in a panel of 22 patients after they became resistant to combined cisplatin and fludarabine treatment (Kim et al., 2011).
  
  
Entity Non-small cell lung cancer (NSCLC)
Note Chromosomal aberrations in 12q13 region are frequent in NSCLC, where there can be either loss of heterozygocity or amplification, sometimes coupled with unbalanced translocation. eIF4B expression is significantly higher in NSCLC tumours showing this kind of alteration (Liang et al., 2013). Synergistic effect of mTOR and MEK inhibitors in NSCLC cell lines is correlated with significant decrease in eIF4B phosphorylation (Zou et al., 2012).
  
  
Entity Oral squamous cell carcinoma
Note Activation of Laminin γ2 by eIF4B is found in pre-malignant oral dysplasia, where eIF4B is activated by ERK/MAP kinase pathway (Degen et al., 2012). Laminin γ2 levels remain high in oral squamous cell carcinoma, although eIF4B has not been studied in this context.
  
  
Entity Prostatic cancer
Note In Prostatic carcinoma, eIF4B phosphorylation by Pim2 leads to resistance to apoptosis (Ren et al., 2013).
  
  
Entity Lymphangioleiomyomatosis
Note eIF4B phosphorylation increased following activation of mTOR pathway in lymphangioleiomyomatosis (Gu et al., 2013).
  
  
Entity Diffuse large B-cell lymphoma (DLBCL)
Note eIF4B is up-regulated following activation of mTOR pathway in DLBCL and, in turn, activates translation of proteins involved in DNA repair and inhibition of apoptosis. Elevated eIF4B level was shown to be poor prognosis in DLBCL (Horvilleur et al., 2013).
  
  
Entity Various cancers
Note Finally, amplification, duplication and deletion of 12q13 have been described in different cancers including sarcoma, glioma, bladder carcinoma or anaplastic lymphoma without direct involvement of eIF4B.
  

To be noted

Doctors Thomas Sbarrato and Emilie Horvilleur contributed equally to this work.

Bibliography

A Saccharomyces cerevisiae homologue of mammalian translation initiation factor 4B contributes to RNA helicase activity.
Altmann M, Muller PP, Wittmer B, Ruchti F, Lanker S, Trachsel H.
EMBO J. 1993 Oct;12(10):3997-4003.
PMID 8404865
 
Wheat germ translation initiation factor eIF4B affects eIF4A and eIFiso4F helicase activity by increasing the ATP binding affinity of eIF4A.
Bi X, Ren J, Goss DJ.
Biochemistry. 2000 May 16;39(19):5758-65.
PMID 10801326
 
Disruption of the interaction of mammalian protein synthesis eukaryotic initiation factor 4B with the poly(A)-binding protein by caspase- and viral protease-mediated cleavages.
Bushell M, Wood W, Carpenter G, Pain VM, Morley SJ, Clemens MJ.
J Biol Chem. 2001 Jun 29;276(26):23922-8. Epub 2001 Mar 23.
PMID 11274152
 
Wheat eukaryotic initiation factor 4B organizes assembly of RNA and eIFiso4G, eIF4A, and poly(A)-binding protein.
Cheng S, Gallie DR.
J Biol Chem. 2006 Aug 25;281(34):24351-64. Epub 2006 Jun 27.
PMID 16803875
 
MAPK/ERK-dependent translation factor hyperactivation and dysregulated laminin γ2 expression in oral dysplasia and squamous cell carcinoma.
Degen M, Natarajan E, Barron P, Widlund HR, Rheinwald JG.
Am J Pathol. 2012 Jun;180(6):2462-78. doi: 10.1016/j.ajpath.2012.02.028. Epub 2012 Apr 28.
PMID 22546478
 
Recognition of polyadenylate RNA by the poly(A)-binding protein.
Deo RC, Bonanno JB, Sonenberg N, Burley SK.
Cell. 1999 Sep 17;98(6):835-45.
PMID 10499800
 
RNA-stimulated ATPase activity of eukaryotic initiation factors.
Grifo JA, Abramson RD, Satler CA, Merrick WC.
J Biol Chem. 1984 Jul 10;259(13):8648-54.
PMID 6145716
 
New initiation factor activity required for globin mRNA translation.
Grifo JA, Tahara SM, Morgan MA, Shatkin AJ, Merrick WC.
J Biol Chem. 1983 May 10;258(9):5804-10.
PMID 6853548
 
Integration of mTOR and estrogen-ERK2 signaling in lymphangioleiomyomatosis pathogenesis.
Gu X, Yu JJ, Ilter D, Blenis N, Henske EP, Blenis J.
Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):14960-5. doi: 10.1073/pnas.1309110110. Epub 2013 Aug 27.
PMID 23983265
 
mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events.
Holz MK, Ballif BA, Gygi SP, Blenis J.
Cell. 2005 Nov 18;123(4):569-80.
PMID 16286006
 
A role for eukaryotic initiation factor 4B overexpression in the pathogenesis of diffuse large B-cell lymphoma.
Horvilleur E, Sbarrato T, Hill K, Spriggs RV, Screen M, Goodrem PJ, Sawicka K, Chaplin LC, Touriol C, Packham G, Potter KN, Dirnhofer S, Tzankov A, Dyer MJ, Bushell M, MacFarlane M, Willis AE.
Leukemia. 2014 May;28(5):1092-102. doi: 10.1038/leu.2013.295. Epub 2013 Oct 18.
PMID 24135829
 
A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation.
Imataka H, Gradi A, Sonenberg N.
EMBO J. 1998 Dec 15;17(24):7480-9.
PMID 9857202
 
Inhibition of protein synthesis in apoptosis: differential requirements by the tumor necrosis factor alpha family and a DNA-damaging agent for caspases and the double-stranded RNA-dependent protein kinase.
Jeffrey IW, Bushell M, Tilleray VJ, Morley S, Clemens MJ.
Cancer Res. 2002 Apr 15;62(8):2272-80.
PMID 11956083
 
A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.
Kim HK, Choi IJ, Kim CG, Kim HS, Oshima A, Michalowski A, Green JE.
PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
PMID 21364753
 
Pushing the limits of the scanning mechanism for initiation of translation.
Kozak M.
Gene. 2002 Oct 16;299(1-2):1-34. (REVIEW)
PMID 12459250
 
Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation.
Lamphear BJ, Kirchweger R, Skern T, Rhoads RE.
J Biol Chem. 1995 Sep 15;270(37):21975-83.
PMID 7665619
 
Dissociation of double-stranded polynucleotide helical structures by eukaryotic initiation factors, as revealed by a novel assay.
Lawson TG, Lee KA, Maimone MM, Abramson RD, Dever TE, Merrick WC, Thach RE.
Biochemistry. 1989 May 30;28(11):4729-34.
PMID 2548591
 
Analysis of 20 genes at chromosome band 12q13: RACGAP1 and MCRS1 overexpression in nonsmall-cell lung cancer.
Liang Y, Liu M, Wang P, Ding X, Cao Y.
Genes Chromosomes Cancer. 2013 Mar;52(3):305-15. doi: 10.1002/gcc.22030. Epub 2012 Dec 8.
PMID 23225332
 
Gene expression profiling of precursor T-cell lymphoblastic leukemia/lymphoma identifies oncogenic pathways that are potential therapeutic targets.
Lin YW, Aplan PD.
Leukemia. 2007 Jun;21(6):1276-84. Epub 2007 Apr 12.
PMID 17429429
 
Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation.
Marintchev A, Edmonds KA, Marintcheva B, Hendrickson E, Oberer M, Suzuki C, Herdy B, Sonenberg N, Wagner G.
Cell. 2009 Feb 6;136(3):447-60. doi: 10.1016/j.cell.2009.01.014.
PMID 19203580
 
The translation initiation factor eIF-4B contains an RNA-binding region that is distinct and independent from its ribonucleoprotein consensus sequence.
Methot N, Pause A, Hershey JW, Sonenberg N.
Mol Cell Biol. 1994 Apr;14(4):2307-16.
PMID 8139536
 
In vitro RNA selection identifies RNA ligands that specifically bind to eukaryotic translation initiation factor 4B: the role of the RNA remotif.
Methot N, Pickett G, Keene JD, Sonenberg N.
RNA. 1996a Jan;2(1):38-50.
PMID 8846295
 
A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3.
Methot N, Song MS, Sonenberg N.
Mol Cell Biol. 1996b Oct;16(10):5328-34.
PMID 8816444
 
The 5'-7-methylguanosine cap on eukaryotic mRNAs serves both to stimulate canonical translation initiation and to block an alternative pathway.
Mitchell SF, Walker SE, Algire MA, Park EH, Hinnebusch AG, Lorsch JR.
Mol Cell. 2010 Sep 24;39(6):950-62. doi: 10.1016/j.molcel.2010.08.021.
PMID 20864040
 
Two structural domains of initiation factor eIF-4B are involved in binding to RNA.
Naranda T, Strong WB, Menaya J, Fabbri BJ, Hershey JW.
J Biol Chem. 1994 May 20;269(20):14465-72.
PMID 8182051
 
Synergistic activation of eIF4A by eIF4B and eIF4G.
Nielsen KH, Behrens MA, He Y, Oliveira CL, Jensen LS, Hoffmann SV, Pedersen JS, Andersen GR.
Nucleic Acids Res. 2011 Apr;39(7):2678-89. doi: 10.1093/nar/gkq1206. Epub 2010 Nov 26.
PMID 21113024
 
Duplex unwinding and ATPase activities of the DEAD-box helicase eIF4A are coupled by eIF4G and eIF4B.
Ozes, AR, Feoktistova K, Avanzino BC, Fraser CS.
J Mol Biol. 2011 Sep 30;412(4):674-87. doi: 10.1016/j.jmb.2011.08.004. Epub 2011 Aug 5.
PMID 21840318
 
Dominant negative mutants of mammalian translation initiation factor eIF-4A define a critical role for eIF-4F in cap-dependent and cap-independent initiation of translation.
Pause A, Methot N, Svitkin Y, Merrick WC, Sonenberg N.
EMBO J. 1994 Mar 1;13(5):1205-15.
PMID 8131750
 
The roles of individual eukaryotic translation initiation factors in ribosomal scanning and initiation codon selection.
Pestova TV, Kolupaeva VG.
Genes Dev. 2002 Nov 15;16(22):2906-22.
PMID 12435632
 
Human Protein Reference Database and Human Proteinpedia as discovery tools for systems biology.
Prasad TS, Kandasamy K, Pandey A.
Methods Mol Biol. 2009;577:67-79. doi: 10.1007/978-1-60761-232-2_6.
PMID 19718509
 
The over-expression of Pim-2 promote the tumorigenesis of prostatic carcinoma through phosphorylating eIF4B.
Ren K, Gou X, Xiao M, Wang M, Liu C, Tang Z, He W.
Prostate. 2013 Sep;73(13):1462-9. doi: 10.1002/pros.22693. Epub 2013 Jun 27.
PMID 23813671
 
Purification and characterization of a new eukaryotic protein translation factor. Eukaryotic initiation factor 4H.
Richter-Cook NJ, Dever TE, Hensold JO, Merrick WC.
J Biol Chem. 1998 Mar 27;273(13):7579-87.
PMID 9516461
 
Modulation of the helicase activity of eIF4A by eIF4B, eIF4H, and eIF4F.
Rogers GW Jr, Richter NJ, Lima WF, Merrick WC.
J Biol Chem. 2001 Aug 17;276(33):30914-22. Epub 2001 Jun 19.
PMID 11418588
 
Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F.
Rozen F, Edery I, Meerovitch K, Dever TE, Merrick WC, Sonenberg N.
Mol Cell Biol. 1990 Mar;10(3):1134-44.
PMID 2304461
 
Interactions between eIF4AI and its accessory factors eIF4B and eIF4H.
Rozovsky N, Butterworth AC, Moore MJ.
RNA. 2008 Oct;14(10):2136-48. doi: 10.1261/rna.1049608. Epub 2008 Aug 21.
PMID 18719248
 
Control of cell survival and proliferation by mammalian eukaryotic initiation factor 4B.
Shahbazian D, Parsyan A, Petroulakis E, Topisirovic I, Martineau Y, Gibbs BF, Svitkin Y, Sonenberg N.
Mol Cell Biol. 2010 Mar;30(6):1478-85. doi: 10.1128/MCB.01218-09. Epub 2010 Jan 19.
PMID 20086100
 
How does a scanning ribosomal particle move along the 5'-untranslated region of eukaryotic mRNA? Brownian Ratchet model.
Spirin AS.
Biochemistry. 2009 Nov 17;48(45):10688-92. doi: 10.1021/bi901379a.
PMID 19835415
 
Identification of differential proteins in nasopharyngeal carcinoma cells with p53 silence by proteome analysis.
Sun Y, Yi H, Zhang PF, Li MY, Li C, Li F, Peng F, Feng XP, Yang YX, Yang F, Xiao ZQ, Chen ZC.
FEBS Lett. 2007 Jan 9;581(1):131-9. Epub 2006 Dec 13.
PMID 17184779
 
Towards a knowledge-based Human Protein Atlas.
Uhlen M, Oksvold P, Fagerberg L, Lundberg E, Jonasson K, Forsberg M, Zwahlen M, Kampf C, Wester K, Hober S, Wernerus H, Bjorling L, Ponten F.
Nat Biotechnol. 2010 Dec;28(12):1248-50. doi: 10.1038/nbt1210-1248.
PMID 21139605
 
Yeast eIF4B binds to the head of the 40S ribosomal subunit and promotes mRNA recruitment through its N-terminal and internal repeat domains.
Walker SE, Zhou F, Mitchell SF, Larson VS, Valasek L, Hinnebusch AG, Lorsch JR.
RNA. 2013 Feb;19(2):191-207. doi: 10.1261/rna.035881.112. Epub 2012 Dec 12.
PMID 23236192
 
Circularization of mRNA by eukaryotic translation initiation factors.
Wells SE, Hillner PE, Vale RD, Sachs AB.
Mol Cell. 1998 Jul;2(1):135-40.
PMID 9702200
 
14-3-3sigma controls mitotic translation to facilitate cytokinesis.
Wilker EW, van Vugt MA, Artim SA, Huang PH, Petersen CP, Reinhardt HC, Feng Y, Sharp PA, Sonenberg N, White FM, Yaffe MB.
Nature. 2007 Mar 15;446(7133):329-32.
PMID 17361185
 
eIF4B phosphorylation by pim kinases plays a critical role in cellular transformation by Abl oncogenes.
Yang J, Wang J, Chen K, Guo G, Xi R, Rothman PB, Whitten D, Zhang L, Huang S, Chen JL.
Cancer Res. 2013 Aug 1;73(15):4898-908. doi: 10.1158/0008-5472.CAN-12-4277. Epub 2013 Jun 7.
PMID 23749639
 
Activation and up-regulation of translation initiation factor 4B contribute to arsenic-induced transformation.
Zhang Y, Wang Q, Guo X, Miller R, Guo Y, Yang HS.
Mol Carcinog. 2011 Jul;50(7):528-38. doi: 10.1002/mc.20733. Epub 2011 Jan 25.
PMID 21268130
 
The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells.
Zou ZQ, Zhang LN, Wang F, Bellenger J, Shen YZ, Zhang XH.
Mol Med Rep. 2012 Feb;5(2):503-8. doi: 10.3892/mmr.2011.682. Epub 2011 Nov 16.
PMID 22101421
 
AGC kinases regulate phosphorylation and activation of eukaryotic translation initiation factor 4B.
van Gorp AG, van der Vos KE, Brenkman AB, Bremer A, van den Broek N, Zwartkruis F, Hershey JW, Burgering BM, Calkhoven CF, Coffer PJ.
Oncogene. 2009 Jan 8;28(1):95-106. doi: 10.1038/onc.2008.367. Epub 2008 Oct 6.
PMID 18836482
 

Citation

This paper should be referenced as such :
T Sbarrato, E Horvilleur, T Pöyry, AE Willis
EIF4B (eukaryotic translation initiation factor 4B)
Atlas Genet Cytogenet Oncol Haematol. 2015;19(1):4-10.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/EIF4BID53571ch12q13.html


External links

Nomenclature
HGNC (Hugo)EIF4B   3285
Cards
AtlasEIF4BID53571ch12q13
Entrez_Gene (NCBI)EIF4B  1975  eukaryotic translation initiation factor 4B
AliasesEIF-4B; PRO1843
GeneCards (Weizmann)EIF4B
Ensembl hg19 (Hinxton)ENSG00000063046 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000063046 [Gene_View]  chr12:53006258-53042215 [Contig_View]  EIF4B [Vega]
ICGC DataPortalENSG00000063046
TCGA cBioPortalEIF4B
AceView (NCBI)EIF4B
Genatlas (Paris)EIF4B
WikiGenes1975
SOURCE (Princeton)EIF4B
Genetics Home Reference (NIH)EIF4B
Genomic and cartography
GoldenPath hg38 (UCSC)EIF4B  -     chr12:53006258-53042215 +  12q13.13   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)EIF4B  -     12q13.13   [Description]    (hg19-Feb_2009)
EnsemblEIF4B - 12q13.13 [CytoView hg19]  EIF4B - 12q13.13 [CytoView hg38]
Mapping of homologs : NCBIEIF4B [Mapview hg19]  EIF4B [Mapview hg38]
OMIM603928   
Gene and transcription
Genbank (Entrez)AB076839 AK092188 AK222528 AK293731 AK299329
RefSeq transcript (Entrez)NM_001300821 NM_001330654 NM_001417 NM_018507
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)EIF4B
Cluster EST : UnigeneHs.702041 [ NCBI ]
CGAP (NCI)Hs.702041
Alternative Splicing GalleryENSG00000063046
Gene ExpressionEIF4B [ NCBI-GEO ]   EIF4B [ EBI - ARRAY_EXPRESS ]   EIF4B [ SEEK ]   EIF4B [ MEM ]
Gene Expression Viewer (FireBrowse)EIF4B [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1975
GTEX Portal (Tissue expression)EIF4B
Human Protein AtlasENSG00000063046-EIF4B [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP23588   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP23588  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP23588
Splice isoforms : SwissVarP23588
PhosPhoSitePlusP23588
Domaine pattern : Prosite (Expaxy)RRM (PS50102)   
Domains : Interpro (EBI)EIF-4B    Nucleotide-bd_a/b_plait    RRM_dom   
Domain families : Pfam (Sanger)RRM_1 (PF00076)   
Domain families : Pfam (NCBI)pfam00076   
Domain families : Smart (EMBL)RRM (SM00360)  
Conserved Domain (NCBI)EIF4B
DMDM Disease mutations1975
Blocks (Seattle)EIF4B
PDB (SRS)1WI8    2J76   
PDB (PDBSum)1WI8    2J76   
PDB (IMB)1WI8    2J76   
PDB (RSDB)1WI8    2J76   
Structural Biology KnowledgeBase1WI8    2J76   
SCOP (Structural Classification of Proteins)1WI8    2J76   
CATH (Classification of proteins structures)1WI8    2J76   
SuperfamilyP23588
Human Protein Atlas [tissue]ENSG00000063046-EIF4B [tissue]
Peptide AtlasP23588
HPRD04892
IPIIPI00012079   IPI00908588   IPI00910983   IPI00798302   IPI00816329   IPI00020570   IPI01022506   IPI01021052   IPI01020867   IPI01021513   IPI01021378   IPI01021182   IPI01021042   
Protein Interaction databases
DIP (DOE-UCLA)P23588
IntAct (EBI)P23588
FunCoupENSG00000063046
BioGRIDEIF4B
STRING (EMBL)EIF4B
ZODIACEIF4B
Ontologies - Pathways
QuickGOP23588
Ontology : AmiGOnuclear-transcribed mRNA poly(A) tail shortening  formation of translation preinitiation complex  cytoplasmic translation  RNA binding  translation initiation factor activity  helicase activity  protein binding  cytosol  polysome  translational initiation  regulation of translational initiation  eukaryotic translation initiation factor 4F complex  RNA strand annealing activity  RNA strand-exchange activity  ribosomal small subunit binding  eukaryotic translation initiation factor 4F complex assembly  
Ontology : EGO-EBInuclear-transcribed mRNA poly(A) tail shortening  formation of translation preinitiation complex  cytoplasmic translation  RNA binding  translation initiation factor activity  helicase activity  protein binding  cytosol  polysome  translational initiation  regulation of translational initiation  eukaryotic translation initiation factor 4F complex  RNA strand annealing activity  RNA strand-exchange activity  ribosomal small subunit binding  eukaryotic translation initiation factor 4F complex assembly  
Pathways : KEGGRNA transport    mTOR signaling pathway    PI3K-Akt signaling pathway    Proteoglycans in cancer   
REACTOMEP23588 [protein]
REACTOME PathwaysR-HSA-72706 [pathway]   
NDEx NetworkEIF4B
Atlas of Cancer Signalling NetworkEIF4B
Wikipedia pathwaysEIF4B
Orthology - Evolution
OrthoDB1975
GeneTree (enSembl)ENSG00000063046
Phylogenetic Trees/Animal Genes : TreeFamEIF4B
HOVERGENP23588
HOGENOMP23588
Homologs : HomoloGeneEIF4B
Homology/Alignments : Family Browser (UCSC)EIF4B
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerEIF4B [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)EIF4B
dbVarEIF4B
ClinVarEIF4B
1000_GenomesEIF4B 
Exome Variant ServerEIF4B
ExAC (Exome Aggregation Consortium)ENSG00000063046
GNOMAD BrowserENSG00000063046
Genetic variants : HAPMAP1975
Genomic Variants (DGV)EIF4B [DGVbeta]
DECIPHEREIF4B [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisEIF4B 
Mutations
ICGC Data PortalEIF4B 
TCGA Data PortalEIF4B 
Broad Tumor PortalEIF4B
OASIS PortalEIF4B [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICEIF4B  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDEIF4B
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch EIF4B
DgiDB (Drug Gene Interaction Database)EIF4B
DoCM (Curated mutations)EIF4B (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)EIF4B (select a term)
intoGenEIF4B
NCG5 (London)EIF4B
Cancer3DEIF4B(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603928   
Orphanet
MedgenEIF4B
Genetic Testing Registry EIF4B
NextProtP23588 [Medical]
TSGene1975
GENETestsEIF4B
Target ValidationEIF4B
Huge Navigator EIF4B [HugePedia]
snp3D : Map Gene to Disease1975
BioCentury BCIQEIF4B
ClinGenEIF4B
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1975
Chemical/Pharm GKB GenePA27713
Clinical trialEIF4B
Miscellaneous
canSAR (ICR)EIF4B (select the gene name)
Probes
Litterature
PubMed79 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineEIF4B
EVEXEIF4B
GoPubMedEIF4B
iHOPEIF4B
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Oct 12 16:21:08 CEST 2017

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.