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Proteasome-Rich PaCS As an Oncofetal UPS Structure Handling Cytosolic Polyubiquitinated Proteins. In Vivo Occurrence, in Vitro Induction, and Biological Role

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2018 Sep 19
PMID 30223470
Citations 1
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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 -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.

Citing Articles

CagA Effector Protein in -Infected Human Gastric Epithelium in Vivo: From Bacterial Core and Adhesion/Injection Clusters to Host Cell Proteasome-Rich Cytosol.

Necchi V, Ricci V, Sommi P, Solcia E Toxins (Basel). 2019; 11(11).

PMID: 31731531 PMC: 6891489. DOI: 10.3390/toxins11110618.

References
1.
Zaarur N, Meriin A, Bejarano E, Xu X, Gabai V, Cuervo A . Proteasome failure promotes positioning of lysosomes around the aggresome via local block of microtubule-dependent transport. Mol Cell Biol. 2014; 34(7):1336-48. PMC: 3993571. DOI: 10.1128/MCB.00103-14. View

2.
Kristiansen M, Deriziotis P, Dimcheff D, Jackson G, Ovaa H, Naumann H . Disease-associated prion protein oligomers inhibit the 26S proteasome. Mol Cell. 2007; 26(2):175-88. DOI: 10.1016/j.molcel.2007.04.001. View

3.
Peschon J, Slack J, Reddy P, Stocking K, Sunnarborg S, Lee D . An essential role for ectodomain shedding in mammalian development. Science. 1998; 282(5392):1281-4. DOI: 10.1126/science.282.5392.1281. View

4.
Tegtmeyer N, Zabler D, Schmidt D, Hartig R, Brandt S, Backert S . Importance of EGF receptor, HER2/Neu and Erk1/2 kinase signalling for host cell elongation and scattering induced by the Helicobacter pylori CagA protein: antagonistic effects of the vacuolating cytotoxin VacA. Cell Microbiol. 2008; 11(3):488-505. DOI: 10.1111/j.1462-5822.2008.01269.x. View

5.
Garcia-Mata R, Gao Y, Sztul E . Hassles with taking out the garbage: aggravating aggresomes. Traffic. 2002; 3(6):388-96. DOI: 10.1034/j.1600-0854.2002.30602.x. View