Abstract
BackgroundThe 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.MethodsThe 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.ResultsThe 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.ConclusionsThe 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.
Highlights
The constituents of stable multiprotein complexes are known to dissociate from the complex to play independent regulatory roles
We have shown the presence of all “heavy” form of translation elongation factors complex (eEF1H) subunits and the absence of subunit A of eEF1H (eEF1A)-sub-complex of eEF1H which consists from eEF1Bα (eEF1B) interaction in the nuclei of lung adenocarcinoma A549 cells
Expression of the mRNAs coding for eEF1H subunits in the human lung carcinoma tissue The expression of mRNAs coding for eEF1A1, eEF1Bα, eEF1Bβ and eEF1Bγ in human lung cancer was assessed by Northern blot analysis of 25 clinical tumor specimens
Summary
The constituents of stable multiprotein complexes are known to dissociate from the complex to play independent regulatory roles. Living cells present a significant pool of proteins bound together in stable complexes to perform various biological functions Forced dissociation of such complexes is important for response of the cell to some extracellular stimuli. Eukaryotic eEF1B that consists of the scaffold (eEF1Bγ) and two catalytic (eEF1Bα and eEF1Bβ) subunits, catalyzes GDP/GTP exchange in the eEF1A molecule [11]. Apart from their main role in translation, the eEF1H subunits have been reported to be involved in different processes unrelated to the translational apparatus. It remains unclear if the cancer-induced overexpression of the eEF1B subunits is coordinated, or an increase of each subunit occurs independently
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