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Intracellular proteolysis

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TAG: intracellular proteolysis, protein degradation, proteasome, Ubiquitin-Proteasome System, class I antigenic presentation, proteotoxicity

In living cells, proteins are continuously subjected to synthesis and degradation processes aimed at adapting the proteome as quickly as possible to any change in the metabolic needs of the cell itself. In particular, each cell needs to remove proteins whose function is no longer required at that time (e.g. regulatory proteins or transcription factors), damaged proteins or which present any type of alteration or modification that could prove potentially dangerous or toxic, propeptides from inactive precursors, and proteins from which to obtain amino acids to be used as an energy source in case of insufficient caloric intake with the diet. In eukaryotic cells the great majority of intracellular proteins are hydrolyzed by the 26S proteasome, a large (2.4 MDa) multimeric protease abundantly expressed in the nucleus and cytosol. The central core of the 26S proteasome consists of the 20S proteolytic particle, at the two free ends of which may associate various regulatory complexes (e.g. 19S, PA28alpha/beta, PA28gamma, PA200) which perform the task of regulating and modifying the functioning of the protease in different ways. In fact, proteasomes are involved in the regulation of a large number of physiological and pathological cellular processes, such as immune responses (both humoral and cell-mediated), regulation of the cell cycle and apoptosis (whose dysregulation leads to neoplastic transformation), elimination of proteins that are prone to aggregate and precipitate, which if they are not promptly eliminated lead to proteotoxic diseases such as neurodegenerative syndromes. Our laboratory deals with studying in vitro the role of proteasomes in these cellular processes, with particular regard to the molecular functions of the various proteasome activators, their functional interactions with the network of molecular chaperones and the effects of their action on potentially bioactive peptides generated during the proteolytic processes.

  • Ricerca Locale, Università degli Studi di Torino 2018, 2019 e 2020

  • Bordini J., Morisi F., Cerruti F., Cascio P., Camaschella C., Ghia P., Campanella A. "Iron causes lipid oxidation and inhibits proteasome function in multiple myeloma plasma cells: a proof of concept for novel combination therapies". Cancers, 2020, 12(4): 970
  • Cerruti, F., Jocollè, G., Salio, C., Oliva, L., Paglietti, L., Alessandria, B., Mioletti, S., Donati, G., Numico, G., Cenci, S., Cascio, P. "Proteasome stress sensitizes malignant pleural mesothelioma cells to bortezomib-induced apoptosis". Scientific Reports, 2017, 7: 17626.
  • Oliva L., Orfanelli U., Resnati M., Raimondi A., Orsi A., Milan E., Palladini G., Milani P., Cerruti F., Cascio P., Casarini S., Rognoni P., Touvier T., Marcatti M., Ciceri F., Mangiacavalli S., Corso A., Merlini G., Cenci S. "The amyloidogenic light chain is a stressor that sensitizes plasma cells to proteasome inhibitor toxicity". Blood, 2017, 129(15): 2132-42.
  • Crespo H., Bertolotti L., Proffiti M., Cascio P., Cerruti F., Acutis P.L., de Andrés D., Reina R., Rosati S. "Low proviral small ruminant lentivirus load as biomarker of natural restriction in goats". Vet. Microbiology, 2016, 192: 152-62.
  • Milan E., Perini T., Resnati M., Orfanelli U., Oliva L., Raimondi A., Cascio P., Bachi A., Marcatti M., Ciceri F., Cenci S. "A plastic SQSTM1/p62-dependent autophagic reserve maintains proteostasis and determines proteasome inhibitor susceptibility in multiple myeloma cells". Autophagy, 2015, 11(7): 1161-78.
  • Raule M., Cerruti F., Cascio P. "Comparative study of the biochemical properties of proteasomes in domestic animals". Veterinary Immunology and Immunopathology, 2015, 166(1-2): 43-9.
  • Cascio P., Cerruti F., Marshall R.S., Raule M., Remelli W., Roberts L.M., Ceriotti A. "A Quantitative Method to Monitor the Efficacy of Inhibitors Against the Chymotrypsin-Like Activity of the Proteasome in Tobacco Leaf Protoplasts". Plant Molecular Biology Reporter, 2015, 33(4): 829-840
  • Cascio P. "PA28αβ: The Enigmatic Magic Ring of the Proteasome?" Biomolecules, 2014, 4: 566-584.
  • Raule M., Cerruti F., Cascio P. "Enhanced rate of degradation of basic proteins by 26S immunoproteasomes". Biochimica et Biophysica Acta - Molecular Cell Research, 2014, 1843: 1942-47.
  • Raule M., Cerruti F., Benaroudj N., Migotti R., Kikuchi J., Bachi A., Navon A., Dittmar G., Cascio P. "PA28αβ Reduces Size and Increases Hydrophilicity of 20S Immunoproteasome Peptide Products". Chemistry and Biology, 2014, 21: 470-480.

  • Laboratori di Biochimica del Dipartimento di Scienze Veterinarie (9630, 9640)

  • Dr. Olivier Coux, Centre de Recherche de Biologie cellulaire de Montpellier (CRBM), CNRS UMR 5237, Université de Montpellier, Montpellier, France.
  • Dr. Sébastien Apcher, Institut Gustave Roussy, Université Paris Sud, Université Paris Saclay, Unité 1015 département d'immunologie , Villejuif, France.
  • Prof. Pierre Goloubinoff, Department of Plant Molecular Biology, Université de Lausanne, Lausanne, Switzerland.
  • Dr. Simone Cenci, Università Vita-Salute San Raffaele, Milano, Italy.
  • Dr. Alessandro Campanella, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.

Last update: 14/02/2022 10:05
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