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Gene Review

EIF3A  -  eukaryotic translation initiation factor 3...

Homo sapiens

Synonyms: EIF3, EIF3S10, Eukaryotic translation initiation factor 3 subunit 10, Eukaryotic translation initiation factor 3 subunit A, KIAA0139, ...
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Disease relevance of EIF3S10


High impact information on EIF3S10

  • Here we report that the 20S proteasome endoproteolytically cleaves the translation initiation factors eIF4G, a subunit of eIF4F, and eIF3a, a subunit of eIF3 [6].
  • Using an immunoperoxidase technique, we stained archival formalin-fixed, paraffin-embedded tissue sections with a monoclonal antibody to the 185-kilodalton protein product (p185) of the HER-2/neu gene [7].
  • We report here that incubation of Rat-1 cells with EGF stimulates tyrosine phosphorylation of p185 [8].
  • Certain amino acid substitutions at position 664 in the transmembrane domain of the neu oncogene-encoded p185 protein product are known to cause malignant transformation of cells [9].
  • The following lines of evidence collectively imply that a candidate ligand of the neu-encoded oncoprotein is secreted by ras-transformed fibroblasts: Medium conditioned by ras transformants is able to induce down-modulation of the neu-encoded p185 and to activate its intrinsic tyrosine kinase activity in vitro [10].

Chemical compound and disease context of EIF3S10

  • The cytoplasmic domain of p180 was found to contain a serine residue(s) that was phosphorylated both in vivo and in vitro by activated protein kinase C. p180 was purified by subjecting solubilized membrane proteins from a human osteosarcoma cell line to immunoaffinity chromatography and gel filtration [11].
  • We have examined the effects of herbimycin A and several analogues on p185, the tyrosine kinase encoded by the erbB2 gene in human breast cancer cells [12].
  • Using the human breast cancer cell lines T47D and MCF7, we found that the arrest of cell growth induced by a steroid-depleted medium was accompanied by a strong increase of c-erbB-2 mRNA and of the c-erbB-2-encoded p185 protein [13].
  • In a screening for new growth factors released by melanoma cells, we found that the p185-phosphorylating capacity of a medium conditioned by a melanoma cell line was due to the secretion of heregulin, a ligand for the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases [14].
  • CONCLUSIONS: Selective and efficient killing of human lung adenocarcinoma cells can be achieved in vitro using c-erbB-2/p185-directed therapy [15].

Biological context of EIF3S10


Anatomical context of EIF3S10

  • The rat embryonal fibroblast cell line (Rat-1) appears to express both EGFR and cellular p185 polypeptides [18].
  • Morphological studies demonstrated that on the cell surface p180 was concentrated in coated pits, whereas inside the cell it was found in endosomes as suggested by its colocalization with the transferrin receptor [11].
  • HL-60/Bcr-Abl cells, with ectopic expression of p185 Bcr-Abl tyrosine kinase (TK), and K562 cells, with endogenous expression of p210 Bcr-Abl TK, display a high degree of resistance against antileukemic drug-induced apoptosis (G. Fang et al., Blood, 96: 2246-2256, 2000) [21].
  • All antisera are highly reactive with a Mr 180,000 (p180) P-glycoprotein contained in membranes of HL60 cells isolated for resistance to vincristine (HL60/Vinc) [22].
  • In this study, we have identified a protein with a molecular mass approximately 180 kDa from rabbit liver cytosol (designated p180), which binds preferentially to the GTP- and guanosine 5'-3-O-(thio)triphosphate-bound forms of Cdc42 [23].

Associations of EIF3S10 with chemical compounds

  • Collectively, these data demonstrate that EGF mediates phosphorylation of p185 at tyrosine as well as serine/threonine through cellular kinases by a receptor-specific mechanism [18].
  • TAb 250 inhibited BT-474 cells but did not alter p185 phosphotyrosine content or increase receptor turnover in these cells [24].
  • Studies with cell lines transfected with erbB2 containing defined deletions indicated that susceptibility to the depletion of p185 by herbimycin and its analogues required the domain encoded by amino acids 751-971 [12].
  • In this article, we tested this hypothesis and investigated whether eIF3 p170 mediates mimosine effect on mRNA translation [25].
  • The purified topoisomerase II migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as two bands with apparent molecular masses of 180 (p180) and 170 kDa (p170); both proteins unknotted P4 DNA in an ATP-dependent manner and displayed amsacrine-stimulated covalent attachment to DNA [26].

Regulatory relationships of EIF3S10


Other interactions of EIF3S10

  • Moreover, the immunohistochemical detection of the transmembrane proteins EGFR, p-185 and p-148 by oncogene overexpression and c-myc oncogene were undertaken in 425 breast cancers [28].
  • L-mimosine, a plant amino acid, can reversibly block mammalian cells at late G1 phase and has been found to affect translation of mRNAs of the cyclin-dependent kinase inhibitor p27, eIF3a (eIF3 p170), and ribonucleotide reductase M2 [29].
  • The cleavage of eIF4G or eIF3a differentially affects the assembly of ribosomal preinitiation complexes on different cellular and viral mRNAs in an in vitro system containing pure components [6].

Analytical, diagnostic and therapeutic context of EIF3S10

  • IMPLICATIONS: The fact that p185 immunoreactivity is rarely heterogeneous is encouraging, both for the potential use of HER-2/neu-related proteins as serum tumor markers and for innovative therapies targeted at p185 expression [7].
  • PATIENTS AND METHODS: Paraffin-embedded tumors from 315 consecutive primary breast cancer patients were screened for c-erbB-2 protein (p185) overexpression by immunohistochemistry using the monoclonal antibody CB11 [30].
  • Using a double monoclonal antibody capture enzyme-linked immunosorbent assay for p185, activity was detected in conditioned media from cultures of SK-BR-3 cells [31].
  • Immunoblotting of the samples prepared from metaphase-synchronized HeLa cells did not have a p180 band, but did exhibit a band with a higher molecular weight [32].
  • In order to physically localize these cells we have stained frozen sections of human thymus with antibodies to CD45RO (p180), and CD45RA (p205/P220), as well as with CD1 and HLA class I to define cortical and medullary areas, respectively [33].


  1. Ligand and p185c-neu density govern receptor interactions and tyrosine kinase activation. Samanta, A., LeVea, C.M., Dougall, W.C., Qian, X., Greene, M.I. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. The epidermal growth factor receptor and the product of the neu protooncogene are members of a receptor tyrosine phosphorylation cascade. Connelly, P.A., Stern, D.F. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  3. Species-specific replication of simian virus 40 DNA in vitro requires the p180 subunit of human DNA polymerase alpha-primase. Stadlbauer, F., Voitenleitner, C., Brückner, A., Fanning, E., Nasheuer, H.P. Mol. Cell. Biol. (1996) [Pubmed]
  4. CGP57148B (STI-571) induces differentiation and apoptosis and sensitizes Bcr-Abl-positive human leukemia cells to apoptosis due to antileukemic drugs. Fang, G., Kim, C.N., Perkins, C.L., Ramadevi, N., Winton, E., Wittmann, S., Bhalla, K.N. Blood (2000) [Pubmed]
  5. Bcr-Abl exerts its antiapoptotic effect against diverse apoptotic stimuli through blockage of mitochondrial release of cytochrome C and activation of caspase-3. Amarante-Mendes, G.P., Naekyung Kim, C., Liu, L., Huang, Y., Perkins, C.L., Green, D.R., Bhalla, K. Blood (1998) [Pubmed]
  6. 20S proteasome differentially alters translation of different mRNAs via the cleavage of eIF4F and eIF3. Baugh, J.M., Pilipenko, E.V. Mol. Cell (2004) [Pubmed]
  7. Stability of HER-2/neu expression over time and at multiple metastatic sites. Niehans, G.A., Singleton, T.P., Dykoski, D., Kiang, D.T. J. Natl. Cancer Inst. (1993) [Pubmed]
  8. EGF-stimulated tyrosine phosphorylation of p185neu: a potential model for receptor interactions. Stern, D.F., Kamps, M.P. EMBO J. (1988) [Pubmed]
  9. Correlation of the structure of the transmembrane domain of the neu oncogene-encoded p185 protein with its function. Brandt-Rauf, P.W., Rackovsky, S., Pincus, M.R. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  10. Experimental approaches to hypothetical hormones: detection of a candidate ligand of the neu protooncogene. Yarden, Y., Weinberg, R.A. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  11. p180, a novel recycling transmembrane glycoprotein with restricted cell type expression. Isacke, C.M., van der Geer, P., Hunter, T., Trowbridge, I.S. Mol. Cell. Biol. (1990) [Pubmed]
  12. Depletion of the erbB-2 gene product p185 by benzoquinoid ansamycins. Miller, P., DiOrio, C., Moyer, M., Schnur, R.C., Bruskin, A., Cullen, W., Moyer, J.D. Cancer Res. (1994) [Pubmed]
  13. Inhibition of c-erbB-2 oncogene expression by estrogens in human breast cancer cells. Dati, C., Antoniotti, S., Taverna, D., Perroteau, I., De Bortoli, M. Oncogene (1990) [Pubmed]
  14. The heregulin/human epidermal growth factor receptor as a new growth factor system in melanoma with multiple ways of deregulation. Stove, C., Stove, V., Derycke, L., Van Marck, V., Mareel, M., Bracke, M. J. Invest. Dermatol. (2003) [Pubmed]
  15. c-erbB-2/p185-directed therapy in human lung adenocarcinoma. Snider, J.M., Bushnell, L.J., Chen, L.C., Lanza, L.A. Ann. Thorac. Surg. (1996) [Pubmed]
  16. Assignment1 of the p150 subunit of the eukaryotic initiation factor 3A gene (EIF3A) to human chromosome band 10q26 by in situ hybridisation. Ensinger, C., Obrist, P., Mikuz, G., Merkx, G., Smeets, D., Bänziger, R., Bachmann, F., Burger, M. Cytogenet. Cell Genet. (1998) [Pubmed]
  17. Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1. Nagase, T., Seki, N., Tanaka, A., Ishikawa, K., Nomura, N. DNA Res. (1995) [Pubmed]
  18. Phosphorylation process induced by epidermal growth factor alters the oncogenic and cellular neu (NGL) gene products. Kokai, Y., Dobashi, K., Weiner, D.B., Myers, J.N., Nowell, P.C., Greene, M.I. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  19. Oncogenic activation of p185neu stimulates tyrosine phosphorylation in vivo. Stern, D.F., Kamps, M.P., Cao, H. Mol. Cell. Biol. (1988) [Pubmed]
  20. Src activity increases and Yes activity decreases during mitosis of human colon carcinoma cells. Park, J., Cartwright, C.A. Mol. Cell. Biol. (1995) [Pubmed]
  21. Geldanamycin and its analogue 17-allylamino-17-demethoxygeldanamycin lowers Bcr-Abl levels and induces apoptosis and differentiation of Bcr-Abl-positive human leukemic blasts. Nimmanapalli, R., O'Bryan, E., Bhalla, K. Cancer Res. (2001) [Pubmed]
  22. Mechanisms of multidrug resistance in HL60 cells: detection of resistance-associated proteins with antibodies against synthetic peptides that correspond to the deduced sequence of P-glycoprotein. Marquardt, D., McCrone, S., Center, M.S. Cancer Res. (1990) [Pubmed]
  23. Identification of a putative effector for Cdc42Hs with high sequence similarity to the RasGAP-related protein IQGAP1 and a Cdc42Hs binding partner with similarity to IQGAP2. McCallum, S.J., Wu, W.J., Cerione, R.A. J. Biol. Chem. (1996) [Pubmed]
  24. Ligand-like effects induced by anti-c-erbB-2 antibodies do not correlate with and are not required for growth inhibition of human carcinoma cells. Shawver, L.K., Mann, E., Elliger, S.S., Dugger, T.C., Arteaga, C.L. Cancer Res. (1994) [Pubmed]
  25. EIF3 p170, a mediator of mimosine effect on protein synthesis and cell cycle progression. Dong, Z., Zhang, J.T. Mol. Biol. Cell (2003) [Pubmed]
  26. Purification of topoisomerase II from amsacrine-resistant P388 leukemia cells. Evidence for two forms of the enzyme. Drake, F.H., Zimmerman, J.P., McCabe, F.L., Bartus, H.F., Per, S.R., Sullivan, D.M., Ross, W.E., Mattern, M.R., Johnson, R.K., Crooke, S.T. J. Biol. Chem. (1987) [Pubmed]
  27. The circulating urokinase plasminogen activator (uPA) and its soluble receptor (suPAR) are not up-regulated by the circulating P105 fraction of the HER-2/neu proto-oncogene: in vivo evidence from patients with advanced non-small cell lung cancer (NSCLC). Jumper, C., Cobos, E., Lox, C. Anticancer Res. (2002) [Pubmed]
  28. Breast preservation versus mastectomy in early breast cancer--1991 update of the GBSG 1--protocol and prognostic factors. The German Breast Cancer Study Group. Sauer, R., Schauer, A., Rauschecker, H.F., Schumacher, M., Gatzemeier, W., Sauerbrei, W., Dunst, J., Seegenschmiedt, M.H., Marx, D. Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]. (1992) [Pubmed]
  29. Modulation of differentiation-related gene 1 expression by cell cycle blocker mimosine, revealed by proteomic analysis. Dong, Z., Arnold, R.J., Yang, Y., Park, M.H., Hrncirova, P., Mechref, Y., Novotny, M.V., Zhang, J.T. Mol. Cell Proteomics (2005) [Pubmed]
  30. Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers. Sjögren, S., Inganäs, M., Lindgren, A., Holmberg, L., Bergh, J. J. Clin. Oncol. (1998) [Pubmed]
  31. The extracellular domain of p185/neu is released from the surface of human breast carcinoma cells, SK-BR-3. Zabrecky, J.R., Lam, T., McKenzie, S.J., Carney, W. J. Biol. Chem. (1991) [Pubmed]
  32. Growth state- and cell cycle-dependent fluctuation in the expression of two forms of DNA topoisomerase II and possible specific modification of the higher molecular weight form in the M phase. Kimura, K., Saijo, M., Ui, M., Enomoto, T. J. Biol. Chem. (1994) [Pubmed]
  33. In situ localization of CD45 isoforms in the human thymus indicates a medullary location for the thymic generative lineage. Gillitzer, R., Pilarski, L.M. J. Immunol. (1990) [Pubmed]
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