title: Prion proteostasis: Hsp104 meets its supporting cast.
abstract: Infectious amyloid forms of the release factor, Sup35, comprise the yeast prion [PSI+]. This protein-based unit of inheritance is an evolutionary capacitor able to release cryptic genetic variation during environmental stress and generate potentially beneficial phenotypes. Genetic data have uncovered a sophisticated proteostasis network that tightly regulates [PSI+] formation, propagation and elimination. Central to this network, is the AAA+ ATPase and protein disaggregase, Hsp104. Shifting the balance of the cytosolic Hsp70:Hsp40 chaperone machinery and associated nucleotide exchange factors also influences the [PSI+] prion cycle. Yet, a precise understanding of how these systems co-operate to directly modulate the protein folding events required for sustainable Sup35 prionogenesis has remained elusive. Here, we spotlight recent advances that begin to clarify this issue. We suggest that the Hsp70:Hsp40 chaperone machinery functions collectively as a rheostat that adjusts Hsp104's basic prion-remodeling activities.
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Sweeny
authors.forename: James
authors.initials: J
authors.lastname: Shorter
mesh_terms: D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology; D006360:Heat-Shock Proteins / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D010454:Peptide Termination Factors; D011328:Prions / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology
chemical_list: D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae