Proteasome-rich PaCS as an oncofetal UPS structure handling cytosolic polyubiquitinated proteins. In vivo occurrence, in vitro induction, and biological role

Enrico Solcia, Vittorio Necchi, Patrizia Sommi, Vittorio Ricci

Research output: Contribution to journalReview articlepeer-review

Abstract

In this article, we outline and discuss available information on the cellular site and mechanism of proteasome interaction with cytosolic polyubiquitinated proteins and heat-shock molecules. The particulate cytoplasmic structure (PaCS) formed by barrel-like particles, closely reproducing in vivo the high-resolution structure of 26S proteasome as isolated in vitro, has been detected in a variety of fetal and neoplastic cells, from living tissue or cultured cell lines. Specific trophic factors and interleukins were found to induce PaCS during in vitro differentiation of dendritic, natural killer (NK), or megakaryoblastic cells, apparently through activation of the MAPK-ERK pathway. Direct interaction of CagA bacterial oncoprotein with proteasome was shown inside the PaCSs of a Helicobacter pylori-infected gastric epithelium, a finding suggesting a role for PaCS in CagA-mediated gastric carcinogenesis. PaCS dissolution and autophagy were seen after withdrawal of inducing factors. PaCS-filled cell blebs and ectosomes were found in some cells and may represent a potential intercellular discharge and transport system of polyubiquitinated antigenic proteins. PaCS differs substantially from the inclusion bodies, sequestosomes, and aggresomes reported in proteinopathies like Huntington or Parkinson diseases, which usually lack PaCS. The latter seems more linked to conditions of increased cell proliferation/differentiation, implying an increased functional demand to the ubiquitin–proteasome system.

Original languageEnglish
Article number2767
JournalInternational Journal of Molecular Sciences
Volume19
Issue number9
DOIs
Publication statusPublished - Sep 14 2018

Keywords

  • Aggresomes
  • Fetal cells
  • Heat-shock proteins
  • Microbial oncogenic proteins
  • Neoplastic cells
  • PaCS
  • Polyubiquitinated proteins
  • Proteasome
  • Sequestosomes
  • Trophic factors/interleukins

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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