Interleukin-1β effect on the endogenous ADP-ribosylation and phosphorylation of eukaryotic elongation factor 2


HACıOSMANOĞLU E., Varol B., Edis B., Bektaş M.

Cytotechnology, vol.68, no.6, pp.2659-2666, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 68 Issue: 6
  • Publication Date: 2016
  • Doi Number: 10.1007/s10616-016-9990-1
  • Journal Name: Cytotechnology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.2659-2666
  • Istanbul University Affiliated: Yes

Abstract

© 2016, Springer Science+Business Media Dordrecht.Eukaryotic elongation factor 2 (eEF2) plays an important role in eukaryotic polypeptide chain elongation. Adenosine diphosphate (ADP)-ribosylation is a post-translational modification reaction that catalyzes the transfer of ADP-ribose group to eEF2 and this causes the inhibition of protein synthesis. Indeed, in the absence of diptheria toxin, endogenous ADP-ribosylation can occur. eEF2 is phosphorylated by eEF2 kinase which prevents binding to ribosomes thus inhibiting its activity. Increase in endogenous ADP-ribosylation level approximately 70–75 % was observed in IL-1β treated HUVECs. Moreover, a 70 % rise of phosphorylation of eEF2 was measured. Alteration of endogenous ADP-ribosylation of eEF2 activity was related with cellular mono-ADP-ribosyltransferases (ADPrT). Increment of endogenous ADP-ribosylation on eEF2 did not seem to occur as a direct effect of IL-1β; it arises from the activation of ADPrT. This 2.5 fold increase was abolished by ADPrT inhibitors. Due to these post-translational modifications, global protein synthesis is inhibited. After dephosphorylation of phospho-eEF2, around 20 % increase in protein synthesis was observed. In conclusion, systemic IL-1β has an important role in the regulation of global protein synthesis.