Abstract
Ubiquitin–proteasome system (UPS) proteins and proteolytic activity are localized in a recently identified cytoplasmic structure characterized by accumulation of barrel-like particles, which is known as the particulate cytoplasmic structure (PaCS). PaCSs have been detected in neoplastic, preneoplastic, chronically infected, and fetal cells, which produce high amounts of misfolded proteins to be degraded by the UPS. Chaperone molecules are crucial in the early stages of handling misfolded proteins; therefore, we searched for these molecules in PaCSs. Heat shock proteins (Hsp), Hsp90, Hsp70, Hsp40, and Bcl-2-associated athanogene (Bag)3 chaperones, although not Bag6, were selectively concentrated into PaCSs of several cell lines and ex vivo fetal or neoplastic cells. Present findings point to PaCSs as an integrated, active UPS center well equipped for metabolism of misfolded proteins, especially in cells under physiological (fetal development) or pathological (neoplasia or inflammation) stress.
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Acknowledgments
This study was supported by Grants from the Italian Ministry of Health (Grant No. RF-2010-2310098) and from Fondazione Cariplo (Grant No. 2012-0529) to Fondazione IRCCS Policlinico San Matteo.
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The authors declare that they have no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.
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Vanoli, A., Necchi, V., Barozzi, S. et al. Chaperone molecules concentrate together with the ubiquitin–proteasome system inside particulate cytoplasmic structures: possible role in metabolism of misfolded proteins. Histochem Cell Biol 144, 179–184 (2015). https://doi.org/10.1007/s00418-015-1327-1
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DOI: https://doi.org/10.1007/s00418-015-1327-1