title: Independent overexpression of the subunits of translation elongation factor complex eEF1H in human lung cancer.
abstract: BACKGROUND
  The constituents of stable multiprotein complexes are known to dissociate from the complex to play independent regulatory roles. The components of translation elongation complex eEF1H (eEF1A, eEF1Bα, eEF1Bβ, eEF1Bγ) were found overexpressed in different cancers. To gain the knowledge about novel cancer-related translational mechanisms we intended to reveal whether eEF1H exists as a single unit or independent subunits in different human cancers.
  
  
  METHODS
  The changes in the expression level of every subunit of eEF1H in the human non-small-cell lung cancer tissues were examined. The localization of eEF1H subunits was assessed by immunohistochemistry methods, subcellular fractionation and confocal microscopy. The possibility of the interaction between the subunits was estimated by co-immunoprecipitation.
  
  
  RESULTS
  The level of eEF1Bβ expression was increased more than two-fold in 36%, eEF1Bγ in 28%, eEF1A in 20% and eEF1Bα in 8% of tumor specimens. The cancer-induced alterations in the subunits level were found to be uncoordinated, therefore the increase in the level of at least one subunit of eEF1H was observed in 52% of samples. Nuclear localization of eEF1Bβ in the cancer rather than distal normal looking tissues was found. In cancer tissue, eEF1A and eEF1Bα were not found in nuclei while all four subunits of eEF1H demonstrated both cytoplasmic and nuclear appearance in the lung carcinoma cell line A549. Unexpectedly, in the A549 nuclear fraction eEF1A lost the ability to interact with the eEF1B complex.
  
  
  CONCLUSIONS
  The results suggest independent functioning of some fraction of the eEF1H subunits in human tumors. The absence of eEF1A and eEF1B interplay in nuclei of A549 cells is a first evidence for non-translational role of nuclear-localized subunits of eEF1B. We conclude the appearance of the individual eEF1B subunits in tumors is a more general phenomenon than appreciated before and thus is a novel signal of cancer-related changes in translation apparatus.
authors.forename: Maryna
authors.initials: M
authors.lastname: Veremieva
authors.forename: Liudmyla
authors.initials: L
authors.lastname: Kapustian
authors.forename: Antonina
authors.initials: A
authors.lastname: Khoruzhenko
authors.forename: Valery
authors.initials: V
authors.lastname: Zakharychev
authors.affiliation: State Key Laboratory of Molecular and Cellular Biology, Institute of Molecular Biology and Genetics NASU, 150 Acad,Zabolotnogo Str,, Kiev 03680, Ukraine. negrutskii@imbg.org.ua.
authors.forename: Boris
authors.initials: B
authors.lastname: Negrutskii
authors.forename: Anna
authors.initials: A
authors.lastname: El'skaya
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D020662:Guanine Nucleotide Exchange Factors / Q000032:analysis* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000235:genetics; D020648:Peptide Elongation Factor 1 / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
chemical_list: C094814:EEF1A1 protein, human; C503234:EEF1A2 protein, human; D020662:Guanine Nucleotide Exchange Factors; D020648:Peptide Elongation Factor 1; D012333:RNA, Messenger; C000599473:eEF1B-alpha protein, human; C000599474:eEF1B-beta protein, human; C000599475:eEF1B-gamma protein, human