title: Cellular strategies for regulating functional and nonfunctional protein aggregation.
abstract: Growing evidence suggests that aggregation-prone proteins are both harmful and functional for a cell. How do cellular systems balance the detrimental and beneficial effect of protein aggregation? We reveal that aggregation-prone proteins are subject to differential transcriptional, translational, and degradation control compared to nonaggregation-prone proteins, which leads to their decreased synthesis, low abundance, and high turnover. Genetic modulators that enhance the aggregation phenotype are enriched in genes that influence expression homeostasis. Moreover, genes encoding aggregation-prone proteins are more likely to be harmful when overexpressed. The trends are evolutionarily conserved and suggest a strategy whereby cellular mechanisms specifically modulate the availability of aggregation-prone proteins to (1) keep concentrations below the critical ones required for aggregation and (2) shift the equilibrium between the monomeric and oligomeric/aggregate form, as explained by Le Chatelier's principle. This strategy may prevent formation of undesirable aggregates and keep functional assemblies/aggregates under control.
authors.affiliation: Centre for High-Throughput Biology, Department of Biochemistry and Molecular Biology, University of British Columbia, East Mall, Vancouver V6T 1Z4, Canada. gsponer@chibi.ubc.ca
authors.forename: Jörg
authors.initials: J
authors.lastname: Gsponer
authors.forename: M Madan
authors.initials: MM
authors.lastname: Babu
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000032:analysis; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions; D011506:Proteins; D020543:Proteome; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins