Influence of Hsp70s and their regulators on yeast prion propagation.
Propagation of yeast prions requires normal abundance and activity of many protein chaperones. Central among them is Hsp70, a ubiquitous and essential chaperone involved in many diverse cellular processes that helps promote proper protein folding and acts as a critical component of several chaperone machines. Hsp70 is regulated by a large cohort of co-chaperones, whose effects on prions are likely mediated through Hsp70. Hsp104 is another chaperone, absent from mammalian cells, that resolubilizes proteins from aggregates. This activity, which minimally requires Hsp70 and its co-chaperone Hsp40, is essential for yeast prion replication. Although much is known about how yeast prions can be affected by altering protein chaperones, mechanistic explanations for these effects are uncertain. We discuss the variety of effects Hsp70 and its regulators have on different prions and how the effects might be due to the many ways chaperones interact with each other and with amyloid.
Masison
Daniel C
DC
Laboratory of Biochemistry and Genetics, National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA. masisond@helix.nih.gov
Kirkland
P Aaron
PA
Sharma
Deepak
D
D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D011328:Prions / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*
D018840:HSP70 Heat-Shock Proteins; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins