title: Proteome response at the edge of protein aggregation.
abstract: Proteins adopt defined structures and are crucial to most cellular functions. Their misfolding and aggregation is associated with numerous degenerative human disorders such as type II diabetes, Huntington's or Alzheimer's diseases. Here, we aim to understand why cells promote the formation of protein foci. Comparison of two amyloid-β-peptide variants, mostly insoluble but differently recruited by the cell (inclusion body versus diffused), reveals small differences in cell fitness and proteome response. We suggest that the levels of oxidative stress act as a sensor to trigger protein recruitment into foci. Our data support a common cytoplasmic response being able to discern and react to the specific properties of polypeptides.
authors: Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK natalia.sanchezd@e-campus.uab.cat.
authors: Natalia
authors: N
authors: Sanchez de Groot
authors: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal.
authors: Ricardo A
authors: RA
authors: Gomes
authors: Department of Neurodegeneration and Restorative Research, University Medical Center Goettingen, Waldweg 33, Goettingen, Germany.
authors: Anna
authors: A
authors: Villar-Pique
authors: Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors: M Madan
authors: MM
authors: Babu
authors: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal.
authors: Ana Varela
authors: AV
authors: Coelho
authors: Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193, Bellaterra (Barcelona), Spain salvador.ventura@uab.cat.
authors: Salvador
authors: S
authors: Ventura
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D066329:Protein Aggregates; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D020543:Proteome / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response
chemical_list: D016229:Amyloid beta-Peptides; D066329:Protein Aggregates; D011506:Proteins; D020543:Proteome; D011993:Recombinant Fusion Proteins
keywords: amyloid-β-peptide; oxidative stress; protein misfolding; proteomic response