The chaperonin CCT interacts with and mediates the correct folding and activity of three subunits of translation initiation factor eIF3: b, i and h

Biochem J. 2014 Mar 1;458(2):213-24. doi: 10.1042/BJ20130979.

Abstract

eIF3 (eukaryotic initiation factor 3) is the largest and most complex eukaryotic mRNA translation factor in terms of the number of protein components or subunits. In mammals, eIF3 is composed of 13 different polypeptide subunits, of which five, i.e. a, b, c, g and i, are conserved and essential in vivo from yeasts to mammals. In the present study, we show that the eukaryotic cytosolic chaperonin CCT [chaperonin containing TCP-1 (tailless complex polypeptide 1)] binds to newly synthesized eIF3b and promotes the correct folding of eIF3h and eIF3i. Interestingly, overexpression of these last two subunits is associated with enhanced translation of specific mRNAs over and above the general enhancement of global translation. In agreement with this, our data show that, as CCT is required for the correct folding of eIF3h and eIF3i subunits, it indirectly influences gene expression with eIF3i overexpression enhancing both cap- and IRES (internal ribosome entry segment)-dependent translation initiation, whereas eIF3h overexpression selectively increases IRES-dependent translation initiation. Importantly, these studies demonstrate the requirement of the chaperonin machinery for the correct folding of essential components of the translational machinery and provide further evidence of the close interplay between the cell environment, cell signalling, cell proliferation, the chaperone machinery and translational apparatus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Chaperonin Containing TCP-1 / metabolism
  • Chaperonin Containing TCP-1 / physiology*
  • Cricetinae
  • Cricetulus
  • Eukaryotic Initiation Factor-3 / chemistry*
  • Eukaryotic Initiation Factor-3 / metabolism*
  • HeLa Cells
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Protein Binding / physiology
  • Protein Folding*
  • Protein Subunits / chemistry*
  • Protein Subunits / metabolism*

Substances

  • Eukaryotic Initiation Factor-3
  • Protein Subunits
  • Chaperonin Containing TCP-1