PAC1-PAC2 proteasome assembly chaperone retains the core α4-α7 assembly intermediates in the cytoplasm

Genes Cells. 2018 Oct;23(10):839-848. doi: 10.1111/gtc.12631. Epub 2018 Aug 22.


The proteasome core particle (CP) is a cytoplasmic and nuclear protease complex and is comprised of two α-rings and two β-rings stacked in order of αββα. The assembly of CP proceeds by ordered recruitment of β-subunits on an α-ring with help of assembly chaperones PAC1-PAC2, PAC3-PAC4, and UMP1. However, the mechanism of α-ring formation remains unsolved. Here, we show that α4, α5, α6, and α7 form a core intermediate as the initial process of α-ring assembly, which requires PAC3-PAC4. α1 and α3 can be incorporated independently into the core α4-α7 intermediate, whereas α2 incorporation is dependent on preceding incorporation of α1. Through these processes, PAC1-PAC2 prevents nonproductive dimerization of α-ring assembly intermediates. We also found that PAC1-PAC2 overrides the effect of nuclear localization signals of α-subunits and retains α-ring assembly intermediates in the cytoplasm. Our results first show a detailed assembly pathway of proteasomal α-ring and explain the mechanism by which CP assembly occurs in the cytoplasm.

Keywords: proteasome; proteasome assembly chaperone; α-ring.

MeSH terms

  • Cytoplasm
  • HEK293 Cells
  • Humans
  • Models, Biological
  • Models, Molecular
  • Molecular Chaperones / metabolism
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteasome Endopeptidase Complex / physiology*
  • Protein Binding
  • Protein Subunits / metabolism
  • RNA, Small Interfering


  • Molecular Chaperones
  • Protein Subunits
  • RNA, Small Interfering
  • PSMA4 protein, human
  • Proteasome Endopeptidase Complex