ABSTRACT
TOLERANCE AND PRION MAINTENANCE SUSAN LINDQUIST* and ERIC C.SCHIRMER
Howard Hughes Medical Institute and the Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S. Maryland Avenue, MC
1028, Chicago, IL 60637, USA
1. Introduction 2. The HSP100/CLP Family of Proteins 2.1. A Large Family of Proteins with Diverse Biological Activities 2.2. Hsp104 Protein Structure 3. Biochemical Properties of Hsp104 3.1. Oligomerization 3.2. ATPase Activity 4. The Role of Hsp104 in Stress Tolerance 4.1. Thermotolerance and the Importance of Hsp104 4.2. The Thermotolerance Function of Hsp104 4.2.1. No Evidence for a Proteolysis Function 4.2.2. A Disassembling/resolubilizing Activity 4.3. Other Stresses 4.4. Combinatorial Stresses 4.5. Physiological Inductions of Tolerance 4.6. Conservation of Tolerance Functions in B-Type Proteins 4.7. The Relationship Between Hsp104 and Other Tolerance Factors 4.7.1. Other Tolerance Factors 4.7.2. Genetic Interactions Between Hsp70 and Hsp104 4.7.3. Genetic Interactions Between Trehalose Synthase and Hsp104 5. Hsp104’s Interaction with a Yeast Prion 5.1. A Role for Hsp104 During Normal Growth 5.2. The Prion Hypothesis 5.3. The Relationship Between [PSI+] And Sup35 5.4. The Role of Hsp104 in the Maintenance of [PSI+] 5.4.1. Overexpression of HSP104 Cures [PSI+] 5.4.2. Deletion of HSP104 Cures [PSI+] 5.4.3. Hsp104 and Sup35 Aggregation in Vivo
1. INTRODUCTION
The gene encoding Hsp104 from Saccharomyces cerevisiae was first cloned in an effort to decipher the mechanisms that cells employ to survive a variety of toxic conditions (Sanchez and Lindquist, 1990). Hsp104 is expressed at a low level under most growth conditions, but it is strongly induced by a variety of environmental stresses (Figure 1 and Sanchez et al., 1992). The protein proved to play a key role in helping cells survive many of these stresses, particularly under the most extreme conditions (Sanchez and Lindquist, 1990; Sanchez et al., 1992; Lindquist et al., 1995). Recent work indicates that, unlike many other Hsp chaperones, Hsp104 has little or no capacity to prevent the aggregation of denatured proteins. Nor does it promote the forward folding of denatured proteins. Rather, Hsp 104 helps to disentangle partially aggregated, stress damaged proteins so that they can be refolded by other chaperone systems in the cell (Parsell et al., 1994b; Glover and Lindquist, 1998).
