title: Chaperone molecules concentrate together with the ubiquitin-proteasome system inside particulate cytoplasmic structures: possible role in metabolism of misfolded proteins.
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.
authors.affiliation: Pathologic Anatomy Section, Department of Diagnostic Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vanoli
authors.forename: Vittorio
authors.initials: V
authors.lastname: Necchi
authors.forename: Serena
authors.initials: S
authors.lastname: Barozzi
authors.forename: Rachele
authors.initials: R
authors.lastname: Manca
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
authors.forename: Enrico
authors.initials: E
authors.lastname: Solcia
mesh_terms: D045744:Cell Line, Tumor; D022083:Cytoplasmic Structures / Q000737:chemistry / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D018832:Molecular Chaperones / Q000032:analysis* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017510:Protein Folding; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: C492980:BAG2 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex