Skip to main content

eIF3 Regulation of Protein Synthesis, Tumorigenesis, and Therapeutic Response

  • Protocol
  • First Online:
Eukaryotic Transcriptional and Post-Transcriptional Gene Expression Regulation

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1507))

Abstract

Translation initiation is the rate-limiting step of protein synthesis and highly regulated. Eukaryotic initiation factor 3 (eIF3) is the largest and most complex initiation factor consisting of 13 putative subunits. A growing number of studies suggest that eIF3 and its subunits may represent a new group of proto-oncogenes and associates with prognosis. They regulate translation of a subset of mRNAs involved in many cellular processes including proliferation, apoptosis, DNA repair, and cell cycle. Therefore, unveiling the mechanisms of eIF3 action in tumorigenesis may help identify attractive targets for cancer therapy. Here, we describe a series of methods used in the study of eIF3 function in regulating protein synthesis, tumorigenesis, and cellular response to therapeutic treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hershey JWB, Miyamoto S (2000) Translational control and cancer. In: Sonenberg N, Hershey JWB, Mathews MB (eds) Translational control of gene expression. Cold Spring Harbor Laboratories Press, New York, pp 637–654

    Google Scholar 

  2. Silvera D, Formenti SC, Schneider RJ (2010) Translational control in cancer. Nat Rev Cancer 10(4):254–266. doi:10.1038/nrc2824

    Article  CAS  PubMed  Google Scholar 

  3. Yin JY, Dong Z, Liu ZQ, Zhang JT (2011) Translational control gone awry: a new mechanism of tumorigenesis and novel targets of cancer treatments. Biosci Rep 31(1):1–15. doi:10.1042/BSR20100077, BSR20100077 [pii]

    Article  CAS  PubMed  Google Scholar 

  4. Ruggero D (2013) Translational control in cancer etiology. Cold Spring Harb Perspect Biol 5(2). doi:10.1101/cshperspect.a012336

    Google Scholar 

  5. Bhat M, Robichaud N, Hulea L, Sonenberg N, Pelletier J, Topisirovic I (2015) Targeting the translation machinery in cancer. Nat Rev Drug Discov 14(4):261–278. doi:10.1038/nrd4505

    Article  CAS  PubMed  Google Scholar 

  6. Sonenberg N, Hershey JWB, Mathews M (2000) Translational control of gene expression, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

    Google Scholar 

  7. Hershey JW (2015) The role of eIF3 and its individual subunits in cancer. Biochim Biophys Acta 1849(7):792–800. doi:10.1016/j.bbagrm.2014.10.005

    Article  CAS  PubMed  Google Scholar 

  8. Dong Z, Zhang JT (2006) Initiation factor eIF3 and regulation of mRNA translation, cell growth, and cancer. Crit Rev Oncol Hematol 59(3):169–180

    Article  PubMed  Google Scholar 

  9. Shen J, Yin JY, Li XP, Liu ZQ, Wang Y, Chen J, Qu J, Xu XJ, McLeod HL, He YJ, Xia K, Jia YW, Zhou HH (2014) The prognostic value of altered eIF3a and its association with p27 in non-small cell lung cancers. PLoS One 9(4), e96008. doi:10.1371/journal.pone.0096008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Pincheira R, Chen Q, Huang Z, Zhang JT (2001) Two subcellular localizations of eIF3 p170 and its interaction with membrane-bound microfilaments: implications for alternative functions of p170. Eur J Cell Biol 80(6):410–418

    Article  CAS  PubMed  Google Scholar 

  11. Qi J, Dong Z, Liu J, Zhang JT (2014) EIF3i promotes colon oncogenesis by regulating COX-2 protein synthesis and beta-catenin activation. Oncogene 33(32):4156–4163. doi:10.1038/onc.2013.397

    Article  CAS  PubMed  Google Scholar 

  12. Liu Z, Dong Z, Yang Z, Chen Q, Pan Y, Yang Y, Cui P, Zhang X, Zhang JT (2007) Role of eIF3a (eIF3 p170) in intestinal cell differentiation and its association with early development. Differentiation 75(7):652–661. doi:10.1111/j.1432-0436.2007.00165.x, DIF165 [pii]

    Article  CAS  PubMed  Google Scholar 

  13. Dong Z, Liu LH, Han B, Pincheira R, Zhang JT (2004) Role of eIF3 p170 in controlling synthesis of ribonucleotide reductase M2 and cell growth. Oncogene 23(21):3790–3801

    Article  CAS  PubMed  Google Scholar 

  14. Yin JY, Shen J, Dong ZZ, Huang Q, Zhong MZ, Feng DY, Zhou HH, Zhang JT, Liu ZQ (2011) Effect of eIF3a on response of lung cancer patients to platinum-based chemotherapy by regulating DNA repair. Clin Cancer Res 17(13):4600–4609. doi:10.1158/1078-0432.CCR-10-2591, 1078-0432.CCR-10-2591 [pii]

    Article  CAS  PubMed  Google Scholar 

  15. Zhang L, Pan X, Hershey JW (2007) Individual overexpression of five subunits of human translation initiation factor eIF3 promotes malignant transformation of immortal fibroblast cells. J Biol Chem 282(8):5790–5800. doi:10.1074/jbc.M606284200, M606284200 [pii]

    Article  CAS  PubMed  Google Scholar 

  16. Wang H, Ru Y, Sanchez-Carbayo M, Wang X, Kieft JS, Theodorescu D (2013) Translation initiation factor eIF3b expression in human cancer and its role in tumor growth and lung colonization. Clin Cancer Res 19(11):2850–2860. doi:10.1158/1078-0432.CCR-12-3084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Rasmussen SB, Kordon E, Callahan R, Smith GH (2001) Evidence for the transforming activity of a truncated Int6 gene, in vitro. Oncogene 20(38):5291–5301. doi:10.1038/sj.onc.1204624

    Article  CAS  PubMed  Google Scholar 

  18. Mayeur GL, Hershey JW (2002) Malignant transformation by the eukaryotic translation initiation factor 3 subunit p48 (eIF3e). FEBS Lett 514(1):49–54

    Article  CAS  PubMed  Google Scholar 

  19. Shi J, Kahle A, Hershey JW, Honchak BM, Warneke JA, Leong SP, Nelson MA (2006) Decreased expression of eukaryotic initiation factor 3f deregulates translation and apoptosis in tumor cells. Oncogene 25(35):4923–4936. doi:10.1038/sj.onc.1209495

    Article  CAS  PubMed  Google Scholar 

  20. Zhang L, Smit-McBride Z, Pan X, Rheinhardt J, Hershey JW (2008) An oncogenic role for the phosphorylated h-subunit of human translation initiation factor eIF3. J Biol Chem 283(35):24047–24060. doi:10.1074/jbc.M800956200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang YW, Lin KT, Chen SC, Gu DL, Chen CF, Tu PH, Jou YS (2013) Overexpressed-eIF3I interacted and activated oncogenic Akt1 is a theranostic target in human hepatocellular carcinoma. Hepatology 58(1):239–250. doi:10.1002/hep.26352

    Article  CAS  PubMed  Google Scholar 

  22. Ahlemann M, Zeidler R, Lang S, Mack B, Munz M, Gires O (2006) Carcinoma-associated eIF3i overexpression facilitates mTOR-dependent growth transformation. Mol Carcinog 45(12):957–967. doi:10.1002/mc.20269

    Article  CAS  PubMed  Google Scholar 

  23. Chen G, Burger MM (1999) p150 expression and its prognostic value in squamous-cell carcinoma of the esophagus. Int J Cancer 84(2):95–100

    Article  CAS  PubMed  Google Scholar 

  24. Dellas A, Torhorst J, Bachmann F, Banziger R, Schultheiss E, Burger MM (1998) Expression of p150 in cervical neoplasia and its potential value in predicting survival. Cancer 83(7):1376–1383

    Article  CAS  PubMed  Google Scholar 

  25. Chen G, Burger MM (2004) p150 overexpression in gastric carcinoma: the association with p53, apoptosis and cell proliferation. Int J Cancer 112(3):393–398

    Article  CAS  PubMed  Google Scholar 

  26. Haybaeck J, O’Connor T, Spilka R, Spizzo G, Ensinger C, Mikuz G, Brunhuber T, Vogetseder A, Theurl I, Salvenmoser W, Draxl H, Banziger R, Bachmann F, Schafer G, Burger M, Obrist P (2010) Overexpression of p150, a part of the large subunit of the eukaryotic translation initiation factor 3, in colon cancer. Anticancer Res 30(4):1047–1055

    CAS  PubMed  Google Scholar 

  27. Liu RY, Dong Z, Liu J, Yin JY, Zhou L, Wu X, Yang Y, Mo W, Huang W, Khoo SK, Chen J, Petillo D, Teh BT, Qian CN, Zhang JT (2011) Role of eIF3a in regulating cisplatin sensitivity and in translational control of nucleotide excision repair of nasopharyngeal carcinoma. Oncogene 30(48):4814–4823. doi:10.1038/onc.2011.189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dong Z, Zhang JT (2003) EIF3 p170, a mediator of mimosine effect on protein synthesis and cell cycle progression. Mol Biol Cell 14(9):3942–3951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lee AS, Kranzusch PJ, Cate JH (2015) eIF3 targets cell-proliferation messenger RNAs for translational activation or repression. Nature 522(7554):111–114. doi:10.1038/nature14267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Pradet-Balade B, Boulme F, Beug H, Mullner EW, Garcia-Sanz JA (2001) Translation control: bridging the gap between genomics and proteomics? Trends Biochem Sci 26(4):225–229, S0968-0004(00)01776-X [pii]

    Article  CAS  PubMed  Google Scholar 

  31. Yin JY, Dong ZZ, Liu RY, Chen J, Liu ZQ, Zhang JT (2013) Translational regulation of RPA2 via internal ribosomal entry site and by eIF3a. Carcinogenesis 34(6):1224–1231. doi:10.1093/carcin/bgt052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Han B, Dong Z, Liu Y, Chen Q, Hashimoto K, Zhang JT (2003) Regulation of constitutive expression of mouse PTEN by the 5′-untranslated region. Oncogene 22(34):5325–5337

    Article  CAS  PubMed  Google Scholar 

  33. Liu Z, Dong Z, Han B, Yang Y, Liu Y, Zhang JT (2005) Regulation of expression by promoters versus internal ribosome entry site in the 5′-untranslated sequence of the human cyclin-dependent kinase inhibitor p27kip1. Nucleic Acids Res 33(12):3763–3771. doi:10.1093/nar/gki680, 33/12/3763 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dong Z, Liu Y, Zhang JT (2005) Regulation of ribonucleotide reductase M2 expression by the upstream AUGs. Nucleic Acids Res 33(8):2715–2725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Han B, Zhang JT (2002) Regulation of gene expression by internal ribosome entry sites or cryptic promoters: the eIF4G story. Mol Cell Biol 22(21):7372–7384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Huang W, Dong Z, Chen Y, Wang F, Wang CJ, Peng H, He Y, Hangoc G, Pollok K, Sandusky G, Fu XY, Broxmeyer HE, Zhang ZY, Liu JY, Zhang JT (2015) Small-molecule inhibitors targeting the DNA-binding domain of STAT3 suppress tumor growth, metastasis and STAT3 target gene expression in vivo. Oncogene 35:783–792. doi:10.1038/onc.2015.215

    Article  CAS  PubMed  Google Scholar 

  37. Zhang Y, Yu JJ, Tian Y, Li ZZ, Zhang CY, Zhang SF, Cao LQ, Qian CY, Zhang W, Zhou HH, Yin JY, Liu ZQ (2015) eIF3a improve cisplatin sensitivity in ovarian cancer by regulating XPC and p27Kip1 translation. Oncotarget 6(28):25441–25451

    Article  PubMed  PubMed Central  Google Scholar 

  38. Johannes G, Carter MS, Eisen MB, Brown PO, Sarnow P (1999) Identification of eukaryotic mRNAs that are translated at reduced cap binding complex eIF4F concentrations using a cDNA microarray. Proc Natl Acad Sci U S A 96(23):13118–13123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

This work was supported in part by the National Natural Science Foundation of China Grants 81573463, Hunan Provincial Natural Science Foundation of China Grant 2015JJ1024, and National Institutes of Health Grant R01 CA140582.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Ji-Ye Yin or Jian-Ting Zhang .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media New York

About this protocol

Cite this protocol

Yin, JY., Dong, Z., Zhang, JT. (2017). eIF3 Regulation of Protein Synthesis, Tumorigenesis, and Therapeutic Response. In: Wajapeyee, N., Gupta, R. (eds) Eukaryotic Transcriptional and Post-Transcriptional Gene Expression Regulation. Methods in Molecular Biology, vol 1507. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6518-2_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6518-2_9

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6516-8

  • Online ISBN: 978-1-4939-6518-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics